RESUMEN
RATIONALE: Several halogenated analogs of benztropine (BZT) have previously been characterized as potent DA uptake inhibitors with behavioral profiles that indicate diminished psychomotor stimulant effects relative to cocaine. In a previous study using a fixed-ratio 10 schedule, two chloro-analogs (3'-Cl-BZT and 4'-Cl-BZT) maintained i.v. self-administration in monkeys but appeared to be weak positive reinforcers. OBJECTIVES: The present experiments were designed to test the hypothesis that 3'-Cl-BZT and 4'-Cl-BZT are relatively weak reinforcers by evaluating reinforcing effects under increased response requirements. To examine further the effect of this halogen substitution on self-administration, 3',4"-diCl-BZT was also evaluated for reinforcing effects. METHODS: Four rhesus monkeys self-administered cocaine (0.03 mg/kg per injection, i.v.) under a fixed-ratio 25 (FR25) schedule until stable responding was established. Saline, various doses of cocaine (0.003-0.2 mg/kg per injection), the BZT analogs (0.012-0.2 mg/kg per injection), GBR 12909 (0.012-0.2 mg/kg per injection), and compounds with known reinforcing effects (d-amphetamine, morphine, pentobarbital, ketamine) were then made available for self-administration. Various doses (0.01-0.3 mg/kg per injection) of the compounds that maintained self-administration under the FR schedule were then substituted for cocaine (0.1 mg/kg per injection) under progressive-ratio (PR) schedules. RESULTS: Reinforcing effects were evident under the FR schedule for 3'-Cl-BZT, 4'-Cl-BZT, GBR 12909, and the control compounds, but not by 3',4"-diCl-BZT. Results with the PR suggested that the rank order of these compounds for their effectiveness as reinforcers was cocaine > GBR 12909 > 3'-Cl-BZT = 4'-Cl-BZT >> 3',4"-diCl-BZT. CONCLUSIONS: This study confirms and extends previous results suggesting that compounds with high DAT affinity can have strong, moderate, weak, or no effectiveness as reinforcers. The mechanisms that may underlie this variation in reinforcing effectiveness of these DAT ligands remain to be established.
Asunto(s)
Benzotropina/análogos & derivados , Benzotropina/farmacología , Inhibidores de Captación de Dopamina/farmacología , Tiempo de Reacción/efectos de los fármacos , Esquema de Refuerzo , Animales , Cocaína/farmacología , Femenino , Macaca mulatta , Masculino , Piperazinas/farmacología , Tiempo de Reacción/fisiología , AutoadministraciónRESUMEN
Operant responding on a progressive ratio (PR) schedule for intravenous cocaine as well as sucrose reinforcement was examined in female rats throughout the reproductive process. Self-administration sessions began before mating, and continued throughout pregnancy and until lactational Day 8; following parturition, litters were present with dams during operant sessions. Physiological changes associated with the reproductive process dramatically altered PR responding for cocaine, while PR responding for sucrose was relatively stable throughout pregnancy and lactation. Female animals exhibited the highest number of responses/session for cocaine during estrus and the 1st trimester of pregnancy and the lowest responding near parturition, with levels only partially recovering during lactation. Dams self-administering cocaine exhibited notably different patterns of maternal behavior in the operant chambers than dams responding for sucrose. Thus, cocaine's reinforcing efficacy may be influenced by (a) the changing physiological profile associated with the reproductive process and (b) competition from the reinforcing properties of offspring during lactation.
Asunto(s)
Conducta Apetitiva/fisiología , Conducta Adictiva/fisiopatología , Estimulantes del Sistema Nervioso Central/administración & dosificación , Cocaína/administración & dosificación , Narcóticos/administración & dosificación , Reproducción/fisiología , Animales , Conducta Apetitiva/efectos de los fármacos , Sacarosa en la Dieta/administración & dosificación , Estro/fisiología , Femenino , Inyecciones Intravenosas , Conducta Materna/efectos de los fármacos , Embarazo , Ratas , Ratas Sprague-Dawley , Esquema de Refuerzo , Recompensa , Autoadministración , Conducta Sexual Animal/fisiologíaRESUMEN
Adult male rats gestationally exposed to cocaine and nonexposed control offspring were examined for differences in operant responding for cocaine and sucrose reinforcement. Offspring were derived from dams that had received subcutaneous injections of 40 mg/kg/3cc cocaine hydrochloride daily on gestational Days 8-20 and nontreated control dams. Although no prenatal treatment differences were seen when the animals lever pressed for sucrose pellets on a progressive-ratio (PR) schedule, adult offspring prenatally exposed to cocaine were observed to exhibit an enhanced rate of cocaine intravenous self-administration on a fixed-ratio 5 (FR-5) schedule along with a marked decrease in break point on the PR reinforcement schedule. These results suggest that the reinforcing efficacy of cocaine may be reduced in animals with a prenatal history of cocaine exposure.
Asunto(s)
Conducta Adictiva , Cocaína/farmacología , Inhibidores de Captación de Dopamina/farmacología , Efectos Tardíos de la Exposición Prenatal , Recompensa , Análisis de Varianza , Animales , Conducta Adictiva/fisiopatología , Condicionamiento Operante/fisiología , Femenino , Masculino , Embarazo , Ratas , Esquema de Refuerzo , Sacarosa/farmacologíaRESUMEN
Previous studies of the effects of ablating the rat's somatosensory cortex on temperature discrimination have yielded negative results. Presently, it was assumed that (1) the rat's face might possess thermal acuity comparable to that found in highly sensitive skin regions of primates, (2) the rat's facial discriminative capacity for thermal differences might be more acute in a cool range well below normal room temperature (24 degrees C), and (3) by using more sensitive procedures and focusing on the effects of damage to the face areas in the rat's somatosensory cortex, disturbances in the capacity to make discriminations between cool stimuli might be revealed that previously went unnoticed. Results of experiments testing these assumptions indicated that rats can use their snouts to make discriminations of 1 degree C or less, that their acuity is better in the cool than in the warm range, and that somatosensory ablations produce moderate to severe disturbances in the capacity to discriminate between cool stimuli but only slight transitory disturbances in this capacity for warm stimuli. Additionally, the results suggest that the sensorimotor cortex may be involved in the rat's thermal discriminative capacity.
Asunto(s)
Aprendizaje Discriminativo/fisiología , Corteza Somatosensorial/fisiología , Temperatura , Análisis de Varianza , Animales , Haplorrinos , Ratas , Valores de ReferenciaRESUMEN
Taste detection performance for representatives of the four taste qualities as a function of stimulus volume (5 x 10(-4) to 1 x 1(-1) ml) was examined in rats using high-precision gustometry, computer-controlled operant procedures, nonparametric signal detection measures of sensitivity and responsivity, and blind control procedures. The overall sensitivity index was positively related to stimulus volume (rs = .60), with optimal detection performance attained with a 5 x 10(-3) ml stimulus volume for salty tastants and a 1 x 10(-2) ml stimulus volume for the other taste qualities. The overall responsivity index was inversely related to stimulus volume (rs = -.47), especially for sour and bitter tastants. These results are consistent with prior observations and demonstrate that operant methods using small tastant samples produce sensitive estimates of the rat's taste detection performance and response bias.
Asunto(s)
Conducta Apetitiva , Atención , Condicionamiento Operante , Umbral Gustativo , Animales , Relación Dosis-Respuesta a Droga , Masculino , Maltosa , Cloruro de Potasio , Psicofísica , Ratas , Cloruro de Sodio , SacarosaRESUMEN
The effects of dietary copper and Vitamin B-6 deficiency on NaCl sensitivity in adult male rats were assessed in separate studies using a double-blind protocol, high-precision gustometry, computer-controlled go/no-go operant procedures and signal detection measures of sensitivity and responsivity. The dietary manipulations reduced plasma copper ion content to 40% of baseline levels in the copper deficient group and plasma 5'-pyridoxalphosphate content to 5% of baseline levels in the Vitamin B-6 deficient group and, as expected, altered hematocrit and hemoglobin levels in both groups. These metabolic changes resulted in increased NaCl preference in the Vitamin B-6 deficient group but did not alter sensitivity or responsivity to NaCl, and similar results were obtained in simple and complex taste discrimination tests. The present results demonstrate that dietary copper and Vitamin B-6 deficiencies do not result in altered taste sensitivity in the adult male rat.