Search

Sprague-Dawley rat pups were deprived of food and/or the dam in experiment 1 for 24 h prior to sacrifice at 4, 10, 16 and 22 days postnatally and analysis of 5-HT, 5-HIAA and 5-HIAA/5-HT ratios in cortex, forebrain minus cortex, and brainstem. Deprivation was observed to increase indoles and their ratio early in life, with the most pronounced effects being observed in early maturing caudal brain regions of neonatal rat pups. These neurochemical effects of deprivation gradually diminished during ontogeny, becoming virtually absent by the age of weaning. In neonates, both deprivation from the dam and food appeared to influence indoleamine levels, whereas absence of food appeared to be primarily influential in older preweanling animals. Ambient temperature during the treatment period did not influence indoles or their ratio in 4- and 10-day-old rat pups, but did begin to influence indoles at 16 days postnatally, an age when homeothermia begins to develop. In experiment 2, it was observed that significant increases in indoleamines were not seen until 16 h of deprivation in 4-day-old rat pups deprived of food, and the dam for 0, 2, 4, 16 or 24 h prior to sacrifice. Possible functional implications of these deprivation-related increases in indoleamines early in ontogeny are discussed.

MDMA (methylenedioxymethamphetamine) is a recreational drug of abuse known as "Ecstasy" which markedly decreases regional brain serotonin (5-HT) content and produces 5-HT nerve terminal degeneration in forebrain areas of the rat. In order to determine the acute and chronic behavioral effects of MDMA, adult rats were given MDMA at 0, 5 or 10 mg/kg, po for 4 consecutive days. Alternatively, parachloroamphetamine (PCA) at 5 mg/kg was administered under the same regimen. Within 30 min after the first dose, the MDMA-treated rats exhibited the serotonin motor syndrome consisting of straub tail and splayed hindlimbs comparable to that seen in the PCA-treated rats. This serotonin motor syndrome, with a duration of about 2 hr, was less pronounced after subsequent doses. At 2-4 wk after the last dose, no significant differences between control and treated rats were seen in emergence, hot plate response, auditory startle response or complex maze behavior even though a significant dose-related decrease (50%) in 5-HT concentration was observed in the frontal cortex and hippocampus of these rats 4 wks after the last dose. Adult female monkeys dosed po with 5 or 10 mg/kg of MDMA twice/day for 4 consecutive days demonstrated no spontaneous behavioral changes or weight loss compared to controls, but forebrain 5-HT concentration was reduced by 80% 1 mon after dosing. These data indicate that at doses only 2-3 times the human dose, MDMA produces significant forebrain 5-HT decreases but does not produce detectable residual behavioral alterations as assessed by these behavioral paradigms.

Sprague-Dawley rat pups were intracisternally injected with 6-hydroxydopamine (6OHDA) or vehicle on postnatal Day 3 and tested for footshock-precipitated wall climbing behavior every 48 hr from postnatal Days 5 through 17. The 6OHDA treatment was observed to lower brain catecholamine levels, particularly in forebrain, and to decrease the incidence of wall climbing. This attenuation in the amount of wall climbing did not appear to be related to any neurotoxin-induced alterations in general motor activity, body weight, or body temperature. It also did not appear that the depression in wall climbing seen in 6OHDA-treated animals was related to an observed neurotoxin-induced increase in shock sensitivity, given that amount of wall climbing was observed to be positively correlated with footshock intensity. These results provide further support that catecholaminergic systems are involved in the elicitation of wall climbing behavior. The 6OHDA treatment did not alter the ontogenetic time course of disappearance of this behavior pattern, suggesting that maturational changes occurring in forebrain catecholaminergic terminals may not be critical for the dissipation of wall climbing following the second postnatal week.

The neurochemical effects of prenatal exposure to dopamine receptor antagonists are as yet poorly characterized. To further examine this problem, pregnant rats were given daily subcutaneous injections of vehicle, 2.5 or 5.0 mg/kg haloperidol over gestational days 6 through 20. Membrane binding of [3H]SCH-23390 (D1-specific) and [3H]spiroperidol (D2-specific in most brain areas) was measured in four regions of the cerebral dopamine system at postnatal day (PND) 30. Dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured in caudate on PND 30 following a d-amphetamine challenge. Prenatal haloperidol exposure reduced [3H]SCH-23390 and [3H]spiroperidol binding in caudate in a dose-dependent manner. [3H]Spiroperidol binding was similarly reduced in nucleus accumbens, but only the low dose (2.5 mg/kg) group showed decreased [3H]SCH-23390 binding in this region. Binding of neither compound was significantly altered in amygdala or frontal cortex. Basal or drug-stimulated levels of caudate DA and DOPAC were unaltered. It is concluded that prenatal haloperidol exposure reduces D1 and D2 binding in some, but not all regions of the forebrain dopamine system.