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RATIONALE: D-Cycloserine (DCS), a partial glutamate N-methyl-D-aspartate (NMDA) receptor agonist, enhances extinction of conditioned fear responding; preliminary data suggest that it may facilitate extinction of drug cue reactivity. OBJECTIVE: This study investigates DCS effects on cocaine cue craving and drug use in cocaine-dependent subjects. METHODS: Thirty-two subjects were randomly assigned to receive (1) DCS only, (2) DCS before sessions 1 and 3, placebo (PBO) before session 2, or (3) PBO only 15-min before each of 3 1-h cocaine cue exposure sessions conducted 1 day apart. Craving ratings were obtained before, during, and after sessions. Drug use and cue-induced craving were assessed 1 week after the last cue session. RESULTS: Repeated presentation of cocaine cues resulted in decreased craving both within and between sessions. DCS did not facilitate extinction learning and may have enhanced craving. The group that received three doses of DCS had significantly higher craving than the PBO group at the baseline ratings taken before sessions 2 and 3, as well as significantly higher cue-induced craving at follow-up. The group that received two doses of DCS did not differ from the PBO group. There were no group differences in postextinction cocaine use. CONCLUSIONS: The reduction of cocaine cue reactivity in the PBO group suggests that the study procedures were sufficient to produce extinction. Under these conditions, DCS did not facilitate extinction and may have enhanced craving. Further studies of glutamatergic agents and extinction in cocaine dependence should include consideration of procedural variables that could have a major impact on study outcomes.
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Trastornos Relacionados con Cocaína/tratamiento farmacológico , Cicloserina/farmacología , Extinción Psicológica/efectos de los fármacos , Miedo/efectos de los fármacos , Adulto , Señales (Psicología) , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Drug craving is an important motivational phenomenon among addicted individuals, and successful management of craving is essential to both the initiation and maintenance of abstinence. Although craving in response to drug cues is common in drug-dependent individuals, it is not universal. At the present time, it is not known why approximately 20-30% of all addicted persons fail to report appreciable craving in laboratory-based cue reactivity studies. This study examined the possibility that alexithymia, a personality attribute characterized by a difficulty identifying and describing emotions, may contribute to the impoverished cue-elicited craving experienced by some addicts. Specifically, we tested the hypothesis that alexithymia, as measured by the Toronto Alexithymia Scale (TAS), would be inversely related to the magnitude of cue-elicited craving obtained in a cue reactivity protocol. Forty methamphetamine-dependent individuals completed the TAS and provided craving ratings for methamphetamine after presentation of methamphetamine-associated cues. Thirteen participants (32%) reported no methamphetamine cue-elicited craving. Contrary to expectation, TAS factor 1 (a measure of difficulty identifying feelings) scores were positively associated with cue-elicited craving. Thus, the results suggest that increasing difficulty-identifying feelings may be associated with higher cue-elicited craving. Clinical implications for this finding are discussed.
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Síntomas Afectivos/fisiopatología , Trastornos Relacionados con Anfetaminas/fisiopatología , Trastornos Relacionados con Anfetaminas/psicología , Motivación , Adolescente , Adulto , Señales (Psicología) , Femenino , Humanos , Individualidad , Masculino , Persona de Mediana Edad , Inventario de PersonalidadRESUMEN
BACKGROUND: Chronic methamphetamine abuse is associated with cognitive deficits that may impede treatment in methamphetamine-dependent patients. Exposure to methamphetamine-related cues can elicit intense craving in chronic users of the drug, but the effects of exposure to drug cues on cognitive performance in these individuals are unknown. OBJECTIVES: This study assessed whether exposure to methamphetamine-related visual cues can elicit craving and/or alter dual task cognitive performance in 30 methamphetamine-dependent subjects and 30 control subjects in the laboratory. METHODS: Reaction time, response errors, and inhibition errors were assessed on an auditory Go-No Go task performed by adult participants (total N = 60) while watching neutral versus methamphetamine-related video cues. Craving was assessed with the Within-Session Rating Scale modified for methamphetamine-dependent subjects. RESULTS: Exposure to methamphetamine-related cues elicited craving only in methamphetamine-dependent subjects. Even in the absence of methamphetamine cues, methamphetamine-dependent subjects exhibited slower reaction times and higher rates of both inhibition and response errors than control subjects did. Upon exposure to methamphetamine cues, rates of both response errors and inhibition errors increased significantly in methamphetamine-dependent subjects. Control subjects exhibited no increase in inhibition errors and only slightly increased rates of response errors upon exposure to methamphetamine cues. Response error rates, but not inhibition error rates or reaction times, during methamphetamine cue exposure were significantly associated with craving scores in methamphetamine-dependent subjects. CONCLUSIONS AND SIGNIFICANCE: Methamphetamine-dependent individuals exhibit cognitive performance deficits that are more pronounced during exposure to methamphetamine-related cues. Interventions that reduce cue reactivity may have utility in the treatment of methamphetamine dependence.
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Trastornos Relacionados con Anfetaminas/psicología , Conducta Adictiva/psicología , Trastornos del Conocimiento/psicología , Adolescente , Adulto , Trastornos Relacionados con Anfetaminas/complicaciones , Conducta Adictiva/complicaciones , Trastornos del Conocimiento/complicaciones , Señales (Psicología) , Humanos , Inhibición Psicológica , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas/estadística & datos numéricos , Estimulación Luminosa/métodos , Desempeño Psicomotor/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacosRESUMEN
Inconsistencies in reports on methamphetamine (METH) associated cognitive dysfunction may be attributed, at least in part, to the diversity of study sample features (eg, clinical and demographic characteristics). The current study assessed cognitive function in a METH-dependent population from rural South Carolina, and the impact of demographic and clinical characteristics on performance. Seventy-one male (28.2%) and female (71.8%) METH-dependent subjects were administered a battery of neurocognitive tests including the Test of Memory Malingering (TOMM), Shipley Institute of Living Scale, Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), Grooved Pegboard Test, California Verbal Learning Test (CVLT), and Wisconsin Card Sorting Test (WCST). Demographic and clinical characteristics (eg, gender, frequency of METH use) were examined as predictors of performance. Subjects scored significantly lower than expected on one test of attention and one of fine motor function, but performed adequately on all other tests. There were no predictors of performance on attention; however, more frequent METH use was associated with better performance for males and worse for females on fine motor skills. The METH-dependent individuals in this population exhibit very limited cognitive impairment. The marked differences in education, Intellectual Quotient (IQ), and gender in our sample when compared to the published literature may contribute to these findings. Characterization of the impact of clinical and/or demographic features on cognitive deficits could be important in guiding the development of treatment interventions.
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Trastornos Relacionados con Anfetaminas/psicología , Trastornos del Conocimiento/psicología , Cognición/efectos de los fármacos , Población Rural/estadística & datos numéricos , Adolescente , Adulto , Trastornos Relacionados con Anfetaminas/complicaciones , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/diagnóstico , Demografía/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Destreza Motora , Pruebas Neuropsicológicas/estadística & datos numéricos , Valor Predictivo de las Pruebas , Caracteres Sexuales , South CarolinaRESUMEN
RATIONALE: Cue-elicited craving and stress responses have been identified as predictors of relapse in drug dependence, but little research exists on the contribution of these factors to marijuana use specifically. OBJECTIVES: The aims of the present study were to evaluate (1) responses to a psychological stressor, (2) responses to marijuana-related cues, and (3) if an exposure to a psychological stressor augmented craving subsequently elicited by marijuana-related cue exposure in marijuana-dependent individuals. METHODS: Subjective (craving, stress), neuroendocrine (adrenocorticotropic hormone (ACTH), cortisol), and physiologic responses to the presentation of neutral and marijuana cues were assessed after randomization to a stress (Trier Social Stress Task (TSST)) or non-stress control condition in marijuana-dependent individuals. Outcome measures were assessed at baseline, post-stressor/pre-neutral cue, post-neutral cue, and post-marijuana cue. RESULTS: Eighty-seven participants completed procedures (stress group, n = 45; non-stress group, n = 42). The stress group had a significant increase over the non-stress group in stress rating (p < 0.001), craving (p = 0.028), cortisol (p < 0.001), and ACTH (p < 0.001) after the completion of the TSST. An increased craving response for all participants was seen following the presentation of the marijuana cues (p = 0.005). Following the TSST or non-stress condition, the non-stress group had an increase in craving to marijuana cues as compared to neutral cues (p = 0.002); an increase in craving was not observed in the stress group (p = 0.404). CONCLUSIONS: Marijuana cue exposure and a social stressor increased craving in marijuana-dependent individuals. Completion of the TSST did not increase craving response to subsequent marijuana cue exposure.
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Señales (Psicología) , Abuso de Marihuana/psicología , Estrés Psicológico/psicología , Adolescente , Hormona Adrenocorticotrópica/sangre , Adulto , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Pruebas Psicológicas , Adulto JovenRESUMEN
Conditioned responses to drug-related environmental cues (such as craving) play a critical role in relapse to drug use. Animal models demonstrate that repeated exposure to drug-associated cues in the absence of drug administration leads to the extinction of conditioned responses, but the few existing clinical trials focused on extinction of conditioned responses to drug-related cues in drug-dependent individuals show equivocal results. The current study examined drug-related cue reactivity and response extinction in a laboratory setting in methamphetamine-dependent individuals. Methamphetamine cue-elicited craving was extinguished during two sessions of repeated (3) within-session exposures to multi-modal (picture, video, and in-vivo) cues, with no evidence of spontaneous recovery between sessions. A trend was noted for a greater attenuation of response in participants with longer (4-7 day) inter-session intervals. These results indicate that extinction of drug cue conditioned responding occurs in methamphetamine-dependent individuals, offering promise for the development of extinction- based treatment strategies.
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Trastornos Relacionados con Anfetaminas/psicología , Aprendizaje por Asociación , Terapia Conductista/métodos , Comportamiento de Búsqueda de Drogas , Extinción Psicológica , Metanfetamina , Adolescente , Adulto , Trastornos Relacionados con Anfetaminas/prevención & control , Estimulantes del Sistema Nervioso Central , Señales (Psicología) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Craving for methamphetamine is commonly reported by heavy users of the drug and may increase the risk of relapse in newly abstinent individuals. Exposure to methamphetamine-associated cues in the laboratory can elicit measureable craving and autonomic reactivity in some individuals with methamphetamine dependence. In this study, clinical and demographic correlates of methamphetamine craving and the optimal conditions for its measurement in the laboratory are explored. METHODS: Subjective (craving) and physiologic (heart rate and skin conductance) reactivity to presentation of methamphetamine-associated photo, video, and paraphernalia cues were evaluated in 43 subjects with methamphetamine dependence. Association of cue reactivity with demographic and clinical characteristics including duration, frequency, amount, and recency of methamphetamine use were assessed. RESULTS: Craving was reported by fewer than half of subjects at baseline and by approximately 70% of subjects after methamphetamine cue exposure. Relative to baseline, subjective craving was increased by all three cue modalities to a similar extent. In general, physiological cue reactivity correlated poorly with cue-induced craving. Craving at baseline was strongly predictive of cue-induced craving. Differences in cue-induced craving were not associated with age, sex, education, employment, treatment status, or number of days using methamphetamine in the 60 days prior to study entry. In contrast, the degree of baseline craving was strongly associated with employment status and the number of days using methamphetamine in the past 60 days. CONCLUSIONS: Cue-induced craving for methamphetamine may be reliably measured in methamphetamine-dependent individuals in the laboratory. Further studies employing the cue reactivity paradigm in methamphetamine dependence are warranted.
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Trastornos Relacionados con Anfetaminas/fisiopatología , Trastornos Relacionados con Anfetaminas/psicología , Conducta Adictiva/fisiopatología , Conducta Adictiva/psicología , Metanfetamina , Adolescente , Adulto , Condicionamiento Psicológico/fisiología , Señales (Psicología) , Femenino , Respuesta Galvánica de la Piel/fisiología , Frecuencia Cardíaca/fisiología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Selección de Paciente , Estimulación Luminosa , Escalas de Valoración PsiquiátricaRESUMEN
UNLABELLED: There are likely to be gender differences in determinants of relapse to drug use following abstinence in cocaine-dependent individuals. Cocaine-dependent women are more likely to attribute relapse to negative emotional states and interpersonal conflict. Cocaine dependence has also been linked to dysregulation of stress response and the hypothalamic pituitary adrenal (HPA) axis which may differ between genders. Subjective and HPA-axis responses to a social evaluative stressor, the Trier Social Stress Test (TRIER), and in vivo cocaine-related cues were examined in the present study. RESULTS: There were no gender differences in magnitude of craving responses to the TRIER or the CUE. Both genders had a greater craving response to the CUE than to the TRIER, but the magnitude of the difference was greater for men than women (p=0.04). Cocaine-dependent subjects, compared to the control group, had significantly higher response throughout the TRIER (p<0.0001) and CUE (p<0.0001) testing sessions. There were no gender differences and no gender by cocaine interaction for ACTH responses to the TRIER, although women had lower baseline ACTH (p=0.049). On the CUE task, in contrast, female cocaine-dependent subjects had a more blunted ACTH response than did the other three groups (p=0.02). Female cocaine-dependent subjects also had a lower odds of a positive cortisol response to the TRIER as compared to the other three groups (OR=0.84, 95% CI=[0.02, 1.01]). During the CUE task, cocaine-dependent subjects had overall higher mean cortisol levels (p=0.0001), and higher odds of demonstrating a positive cortisol response to the CUE (OR=2.61, 95% CI=[1.11, 6.11]). No gender differences were found in ACTH responses to the CUE. The results are reviewed in the context of the existing literature on gender differences in cocaine dependence and potential implications for treatment are discussed.
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Hormona Adrenocorticotrópica/sangre , Trastornos Relacionados con Cocaína/sangre , Trastornos Relacionados con Cocaína/psicología , Señales (Psicología) , Hidrocortisona/sangre , Caracteres Sexuales , Estrés Psicológico/sangre , Adulto , Conducta Adictiva/sangre , Conducta Adictiva/psicología , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Cocaine dependence is a chronic relapsing disorder characterized by periods of abstinence and high rates of return to drug using behavior. Elevated levels of stress have been associated with relapse to cocaine; however, the nature of this association is not well understood. METHODS: The relationship between reactivity to three human laboratory provocations and relapse to cocaine was investigated. Participants were 53 cocaine-dependent individuals who were admitted for a 2-day inpatient stay during which a psychosocial provocation (i.e., the Trier Social Stress Task), a pharmacological provocation (i.e., administration of 1 microg/kg corticotrophin releasing hormone; CRH), and a drug cue exposure paradigm were completed. Adrenocortico-trophic hormone (ACTH), cortisol, heart rate, and subjective cocaine craving and stress were assessed at baseline and at multiple time points post-task. Participants' cocaine use was monitored for approximately 1 month following testing. RESULTS: The majority (72.3%) of participants relapsed to cocaine during the follow-up period. In response to the CRH and drug cue exposure, elevated subjective craving and stress were significant predictors of cocaine use during follow-up. In response to the Trier, attenuated neuroendocrine responses were significant predictors of cocaine use. CONCLUSIONS: The findings provide further evidence of the ability of laboratory paradigms to predict relapse. The observed associations between stress reactivity and subsequent cocaine use highlight the clinical importance of the findings. Predictors of relapse may vary based on the type of provocation utilized. Interventions aimed at normalizing stress response, as measured using laboratory paradigms, may prove useful in relapse prevention.
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Trastornos Relacionados con Cocaína/psicología , Estrés Psicológico/psicología , Hormona Adrenocorticotrópica/sangre , Adulto , Trastornos Relacionados con Cocaína/fisiopatología , Hormona Liberadora de Corticotropina/sangre , Señales (Psicología) , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Estimación de Kaplan-Meier , Masculino , Sistemas Neurosecretores/fisiopatología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Recurrencia , Factores Socioeconómicos , Estrés Psicológico/fisiopatología , Análisis de SupervivenciaRESUMEN
BACKGROUND: D-cycloserine (DCS), a partial glutamate N-methyl-D-aspartic acid (NMDA) receptor agonist, enhances extinction of conditioned fear responding in rodents and facilitates exposure-based learning in humans with anxiety disorders. OBJECTIVES: This preliminary study investigates DCS pretreatment on response to cocaine cues in cocaine-dependent subjects. METHODS: Ten cocaine-dependent subjects were randomly assigned to receive either 50 mg DCS or matching placebo two hours before each of two 1-hour cocaine cue exposure sessions one day apart. HR and craving ratings were obtained before and during cue exposure sessions. RESULTS: There was a trend towards increased craving to cocaine cues in cocaine-dependent individuals after administration of DCS. CONCLUSIONS: The administration of DCS prior to cue exposure sessions may facilitate response activation. SCIENTIFIC SIGNIFICANCE: While facilitation of extinction-based learning by DCS may have therapeutic potential for cocaine dependence, this drug may exhibit a different profile in cocaine-dependent individuals as compared to those with anxiety disorders.
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Conducta Adictiva/tratamiento farmacológico , Trastornos Relacionados con Cocaína/tratamiento farmacológico , Cocaína/farmacología , Señales (Psicología) , Cicloserina/uso terapéutico , Extinción Psicológica/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/agonistas , Adolescente , Adulto , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Proyectos PilotoRESUMEN
OBJECTIVE: A strong association between a history of child abuse and subsequent psychiatric disorders including substance use has been demonstrated. However, few studies have examined the relationship between child abuse and cigarette smoking in individuals without co-occurring psychiatric disorders. In this study, the relationship between severe childhood abuse and smoking were examined in a group of adults without significant psychopathology. METHODS: Participants (N = 57) represent the control group of a larger study of substance dependence. Participants were without major DSM-IV psychopathology, including substance use disorders, major depression, or posttraumatic stress disorder. The Early Trauma Inventory [20] assessed history of exposure to traumatic events prior to age 18. RESULTS: The majority of individuals with, as compared to without, a history of severe child abuse (79% vs. 47%, p = .02) were current cigarette smokers. The odds of smoking was four times as high in participants with versus without a severe childhood abuse history (OR = 4.0, p = 0.04). CONCLUSIONS: Although preliminary, the findings demonstrate a strong link between early childhood trauma and later adult cigarette smoking among individuals without significant substance use or other psychopathology.
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Maltrato a los Niños/estadística & datos numéricos , Fumar/epidemiología , Adulto , Niño , Maltrato a los Niños/psicología , Estudios Transversales , Femenino , Humanos , Acontecimientos que Cambian la Vida , Masculino , Persona de Mediana Edad , Inventario de Personalidad , Riesgo , Fumar/psicologíaRESUMEN
This article represents the proceedings of a symposium at the Research Society on Alcoholism meeting in Santa Barbara, California. The organizers/chairs were Kristine M. Wiren and Deborah A. Finn. Following a brief introduction by Deborah Finn, the presentations were (1) The Importance of Gender in Determining Expression Differences in Mouse Lines Selected for Chronic Ethanol Withdrawal Severity, by Kristine M. Wiren and Joel G. Hashimoto; (2) Sex Differences in Ethanol Withdrawal Involve GABAergic and Stress Systems, by Paul E. Alele and Leslie L. Devaud; (3) The Influence of Sex on Ethanol Consumption and Reward in C57BL/6 Mice, by Kimber L. Price and Lawrence D. Middaugh; and (4) Sex Differences in Alcohol Self-administration in Cynomolgus Monkeys, by Kathleen A. Grant.
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Adaptación Fisiológica/efectos de los fármacos , Alcoholismo/fisiopatología , Encéfalo/efectos de los fármacos , Neuronas/efectos de los fármacos , Refuerzo en Psicología , Adaptación Fisiológica/genética , Delirio por Abstinencia Alcohólica/genética , Delirio por Abstinencia Alcohólica/fisiopatología , Alcoholismo/genética , Alcoholismo/rehabilitación , Animales , Encéfalo/fisiopatología , Mapeo Encefálico , Etanol/efectos adversos , Expresión Génica/efectos de los fármacos , Genotipo , Humanos , Ratones , Ratones Endogámicos , Neuronas/fisiología , Selección Genética , Factores Sexuales , Especificidad de la EspecieRESUMEN
A set of neurotensin[8-13] (NT[8-13]) analogues (KK1-19) has been evaluated in various pre-clinical assays relevant for further development of these compounds as potential antipsychotics. Initial screening of these compounds for induction of hypothermia following systemic (I.V.) injection in rats, an indirect method commonly utilized to measure the central nervous system (CNS) activity of NT[8-13] analogues, identified three peptides, KK1, KK13 and KK14, capable of crossing the blood-brain barrier (BBB). KK1 features 2(S)-azido-7-aminoheptanoic acid (AAHA) in the Arg(8) position and represents the first monosubstituted NT[8-13] analogue that crosses the BBB. KK13 and KK14 both feature AAHA in the Arg(8) position and tert-Leu in the Ile(12) position while KK14 includes a Trp substituted for Tyr(11). When I.P. administered, only the latter two analogues induced a significant hypothermic response. KK13 (1mg/kg) inhibited amphetamine-induced hyperlocomotion after I.P. injection; this assay is highly predictive for potential antipsychotics. Chronic dosing (5mg/kg) of this compound over 5 consecutive days failed to induce hypothermic tolerance while the same dose failed to induce measurable catalepsy. KK13 is thus the first NT[8-13] analogue described to date that demonstrates inhibition of amphetamine-induced hyperlocomotion without inducing catalepsy while maintaining day-to-day hypothermic potency.
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Barrera Hematoencefálica/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Neurotensina/farmacología , Fragmentos de Péptidos/farmacología , Receptores de Neurotensina/metabolismo , Animales , Barrera Hematoencefálica/metabolismo , Relación Dosis-Respuesta a Droga , Hipotermia/inducido químicamente , Hipotermia/metabolismo , Masculino , Actividad Motora/fisiología , Neurotensina/química , Neurotensina/metabolismo , Fragmentos de Péptidos/química , Fragmentos de Péptidos/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Dopamine D1 antagonist effects on behaviors related to obtaining and consuming ethanol remain unclear. The highly selective D1 antagonist ecopipam (SCH 39166), which has no effect on the serotonin system, was used to evaluate the role of D1 receptors in ethanol reward and its potential for treating alcohol abuse by determining its effect on several measures of ethanol reward in C57BL/6 (B6) mice. METHODS: Ecopipam (0.025-0.2 mg/kg) effects on instrumental and contingent consummatory responses and on noncontingent consummatory responses for ethanol and water reward were determined in food-restricted male mice trained to lever-respond for 12% ethanol delivered on a fixed ratio-4 reinforcement schedule. The mice were tested for 15-min sessions under preprandial (high-hunger and low-thirst) and postprandial (low-hunger and high-thirst) test conditions. RESULTS: Ecopipam dose-dependently reduced instrumental and consummatory responses for ethanol and ethanol intake when tested under hunger- or thirst-motivated conditions with free access to water. Under thirst motivation with no access to an alternate fluid source, lever responses for ethanol and water were similar; however, ecopipam reduced responding for ethanol more than responding for water reward. When given concurrent free access to the same fluid delivered for lever pressing, animals made more contacts for ethanol than for water; ecopipam reduced free ethanol but not water contacts. CONCLUSIONS: Ecopipam attenuated ethanol reward at doses that did not affect water reward, indicating an effect independent of reductions in motor system function or general motivation and arousal. Ecopipam also reduced ethanol reward to the same degree under hunger, thirst, or sated conditions, again indicating that it affected ethanol reward at doses that did not grossly affect general motivational states. These data suggest that ecopipam may reduce ethanol reward with few side effects and that it warrants further investigation as a pharmacological tool for treating alcohol abuse.
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Antagonistas de Dopamina/farmacología , Etanol/farmacología , Receptores de Dopamina D1/antagonistas & inhibidores , Recompensa , Animales , Condicionamiento Psicológico/efectos de los fármacos , Condicionamiento Psicológico/fisiología , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Ratones Endogámicos C57BL , Receptores de Dopamina D1/fisiologíaRESUMEN
Although research suggests that ovariectomy (ovx) is detrimental to spatial cognition in young rats, little work has evaluated the cognitive effects of ovx in aged rats. The authors investigated the effects of ovx in aged rats using the water radial-arm maze. In Study 1, young rats and aged rats receiving ovx 1.5 months before testing outperformed aged rats receiving sham surgery or ovx 21 days before testing. In Study 2, young rats and aged rats receiving ovx 2.0 or 6.0 months before testing outperformed aged sham rats. Aged rats exhibited estradiol and elevated progesterone levels comparable to those of young rats. The findings suggest that 1.5-6.0 months, but not 21 days, of ovx improves spatial memory in aged rats. The hypothesis that long-term ovarian hormone loss is detrimental to spatial memory in aged rats was not supported. The authors hypothesize that removal of elevated progesterone levels is related to the ovx-induced cognitive enhancement.
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Envejecimiento/fisiología , Estradiol/sangre , Aprendizaje por Laberinto/fisiología , Progesterona/sangre , Retención en Psicología/fisiología , Percepción Espacial/fisiología , Animales , Cognición/fisiología , Femenino , Ovariectomía , Ratas , Ratas Endogámicas F344 , Conducta Espacial/fisiologíaRESUMEN
Relapse to drug use following prolonged periods of abstinence results, in part, from the ability of contextual cues paired previously with self-administered drug to elicit drug craving and -seeking behavior. Given the popularity of the mouse for the genetic analysis of drug-induced behaviors, a place conditioning model of drug-seeking behavior was used to examine the ability of cocaine (COC) to reinstate extinguished conditioned reward in mice. In a series of experiments, COC place conditioning was produced in male C57BL/6 (B6) mice by four pairings of COC (15 or 25 mg/kg, IP) with the non-preferred compartment of a two-compartment place conditioning apparatus. Following a post-conditioning test (Post-Test), place conditioning was extinguished by repeated testing. The mice were then challenged with one of five COC doses (0, 5, 10, 15 or 25 mg/kg, IP) and allowed free access to both environments. Following extinction, COC injections reinstated place conditioning to 100% or greater, relative to the Post-Test. In a control experiment, mice received either COC or SAL paired with non-preferred compartment and were then challenged with either COC (15 mg/kg, IP) or SAL on the Post-Test. COC-conditioned, but not SAL-conditioned, mice exhibited place conditioning when tested in a COC-free state. Interestingly, COC injection on the Post-Test elicited an increase in approach behavior in both SAL- and COC-conditioned mice and this increase was equivalent to that produced by COC conditioning alone. No direct relationships were observed between the magnitude of place conditioning and either COC-induced or -conditioned locomotor hyperactivity in the non-preferred compartment. Thus, at least two independent processes appear to underlie the ability of a COC injection to elicit approach behavior towards the non-preferred compartment of a biased place conditioning apparatus in mice-reactivation of the conditioned incentive motivational properties of COC-paired cues and elicitation of unconditioned behavioral disinhibition. One or both of these processes sensitizes with the passage of time, increasing the propensity of B6 mice to approach non-preferred environments upon COC re-administration.