Search

We used functional magnetic resonance imaging (fMRI) to investigate the acute effects of a recreational dose (1 mg/kg p.o.) of 3,4-methylenedioxymethamphetamine (MDMA) on regional brain activity in awake, restrained marmoset monkeys. In a second study, magnetic resonance spectroscopy (MRS) and postmortem measurements of serotonin transporter (SERT) binding and serotonin (5-HT) concentrations were used to determine the neurotoxic effects of low (4 x 1 mg/kg p.o.) and high (4 x 10 mg/kg i.m.) doses of MDMA. Several brain areas were significantly activated by the low oral dose of MDMA, including the midbrain raphe nuclei, hippocampus, hypothalamus, amygdala, and the corticostriatal circuit composed of the dorsal thalamus, sensory motor cortex, and basal ganglia. MDMA activated the primary visual cortex under baseline conditions and also enhanced the visual cortical response to photic stimulation. The onset of brain activation correlated well with the rise in plasma MDMA concentrations measured in separate monkeys given the same drug treatment. In the second study, the ratio of N-acetylaspartate (NAA; a putative neuronal marker) to creatine was significantly reduced in the hypothalamus following either MDMA treatment regimen, suggesting a particular vulnerability of this structure to MDMA-induced damage. Monkeys given the high-dose regimen also showed prolonged hyperthermia and reductions in 5-HT and SERT in a number of brain areas. These results are the first to identify the pattern of MDMA-induced brain activation in a nonhuman primate model, and they further suggest that even recreational doses of MDMA may have adverse consequences as indicated by the reduced hypothalamic NAA/creatine ratio.

During adolescence or adulthood, male hamster siblings were divided into control and experimental groups and exposed to periods of either mild or traumatic stress outside their individual nests. Mild stress is the simple exposure to a novel environment while the traumatic stressor is repeated daily subjugation by a dominant hamster. Over adolescence and adulthood, animals had free access to alcohol. The behavior and neuroendocrinology were assessed over these developmental periods in response to these environmental conditions. As adults, animals with a history of traumatic stress in adolescence showed inappropriate and excessive aggressive behavior. Their aggression was context dependent. In the presence of equal size hamsters, they showed little aggression; however, they were excessively aggressive toward smaller, younger animals. Testosterone levels and reproductive behavior were normal after adolescent subjugation; however, release of cortisol during agonistic encounters was suppressed. In comparison, hamsters exposed to chronic social subjugation as adults had low plasma testosterone, reduced reproductive behavior, and exaggerated cortisol release during agonistic encounters. Self-ingestion of alcohol during adolescence enhanced testosterone release around the peripubertal period but reduced plasma testosterone levels in adulthood. Exposure to alcohol as adolescents enhanced aggression in adulthood. These data demonstrate a pronounced difference in behavior and neuroendocrinology between adolescent and adult hamsters in their response to traumatic stress.

These data suggest that shock stress during adolescence increases ETOH consumption and may contribute to an increase in aggression in early adulthood. Interestingly, shock stress without ETOH results in timid behavior in early adulthood. One might speculate that adolescent hamsters "self-medicate" to deal with continuous stress. However, because of the variability between experimental groups, it is necessary to replicate these studies with larger numbers of animals and expand the findings to include blood ETOH concentrations.

In the present study, the ability of high-dose androgens, namely AAS, administered during adolescence to facilitate aggressive behavior in experimental animals was examined. Data from these studies show clearly that exposure to high doses of multiple AAS during adolescent development can predispose animals to intense bouts of aggressive behavior during young adulthood. Specifically, young adult hamsters treated with high doses of AAS throughout adolescence were more likely to attack and bite intruders placed in their home cage than sesame oil (vehicle)-treated control animals. Further, AAS-treated animals displayed a higher intensity of attack during the test period, exhibiting greater than four times the number of attacks/bites of control animals. Given the recent reports of increased incidence of AAS abuse in the adolescent population and the documented stimulatory effects of AAS on aggressive behavior, the study of the behavioral and neurobiological effects of prolonged exposure to AAS during critical phases of development such as adolescence warrants further investigation.