RESUMEN
Previous reports from our laboratory have provided evidence that acute, i.e., concurrent, treatment with selective serotonin reuptake inhibitors (SSRIs) augments the stimulus effects of indoleamine and phenethylamine hallucinogens in the rat. In the present investigation, the acute effects of fluoxetine and citalopram on stimulus control induced by (-)-2,5-dimethoxy-4-methylamphetamine (DOM) were compared with those following subchronic, i.e., 10-day treatment with the SSRIs. Stimulus control was established using DOM (0.56 mg/kg; 75-min pretreatment time) in a group of 11 rats. A two-lever, fixed ratio 10, positively reinforced task with saline controls was employed. The effects of a range of doses of DOM when given alone were compared with those following both acute and subchronic pretreatment with fluoxetine and citalopram in combination with DOM. It was found that acute administration of fluoxetine and citalopram potentiated the stimulus effects of DOM. Furthermore, it was observed that the degree of potentiation was not diminished by treatment with either fluoxetine or citalopram for a period of 10 days. It is concluded that whatever adaptive changes may take place in response to a 10-day period of treatment with either citalopram or fluoxetine, these adaptations are independent of the mechanisms responsible for the potentiation of the stimulus effects of DOM by the SSRIs.
Asunto(s)
Conducta Animal/efectos de los fármacos , Citalopram/farmacología , Condicionamiento Operante/efectos de los fármacos , 2,5-Dimetoxi-4-Metilanfetamina/farmacología , Fluoxetina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Agonistas de Receptores de Serotonina/farmacología , Animales , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Masculino , Ratas , Ratas Endogámicas F344 , Receptores de Serotonina/efectos de los fármacos , Receptores de Serotonina 5-HT1 , Estimulación Química , Factores de TiempoRESUMEN
The present investigation examined the interaction between 2,5-dimethoxy-4-methylamphetamine [DOM] and the selective serotonin reuptake inhibitor [SSRI] citalopram in rats trained with DOM [0.6 mg/kg; 75 min pretreatment time] as a discriminative stimulus. Pretreatment with citalopram at a dose of 1.0 mg/kg shifted the DOM dose response relationship to the left. Unlike previously tested SSRI's, the enhancement of DOM-induced stimulus control occurred in the absence of significant partial substitution by citalopram. DOM brain levels were measured using a GC-MS method both in the presence and absence of citalopram and fluoxetine in order to evaluate the pharmacokinetic contribution to the observed behavioral effect. The data indicated that fluoxetine but not citalopram significantly increased DOM brain levels. It is concluded that the effects of DOM as a discriminative stimulus are potentiated by the acute administration of citalopram and this effect is not mediated by additivity or pharmacokinetic mechanisms.
Asunto(s)
Citalopram/farmacología , 2,5-Dimetoxi-4-Metilanfetamina/farmacología , Aprendizaje Discriminativo/efectos de los fármacos , Fluoxetina/farmacología , Alucinógenos/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , 2,5-Dimetoxi-4-Metilanfetamina/farmacocinética , Animales , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Sinergismo Farmacológico , Cromatografía de Gases y Espectrometría de Masas , Masculino , Ratas , Ratas Endogámicas F344 , Refuerzo en Psicología , Agonistas de Receptores de Serotonina/farmacologíaRESUMEN
Neonatal monosodium glutamate (MSG) treatment has been associated with dysfunctions in stress responses. Therefore, the present study aimed at examining the acoustic startle response (ASR) in MSG-treated rats and the effects of fetal neural transplantation. Male and female rats were given MSG (4 mg/g) or saline on alternate days from days 2-10 after birth. To determine whether fetal transplants could reverse behavioral impairments observed in MSG-treated rats, at 12 days of age MSG-treated rats received either arcuate nucleus (AN), cortical fetal grafts, or sham surgery into the third ventricle. ASR amplitude was measured at 35-40 days of age, and again in adulthood. MSG produced the expected decrease in the density of hypothalamic neuropeptide Y (NPY) and tyrosine hydroxylase (TH) in the AN area. Corticotropin-releasing factor (CRF) neurons/fibers were not affected by MSG. Pituitary atrophy was observed in all MSG rats. We report a permanent increase in the amplitude and reduction in short-term habituation of ASR in all MSG-treated rats. No effect was observed on long-term habituation in male rats. Cortical, but not AN tissue significantly reduced the magnitude of ASR in MSG animals. The results are discussed in terms of the central pathways mediating ASR, in particular hypothalamo-amygdala connections. It is considered that nonspecific factors mediate recovery produced by cortical tissue grafts, as observed in other models of neural transplantation.