Early maternal deprivation-induced modifications in the neurobiological, neurochemical and behavioral profile of adult rats

Early maternal deprivation (MD) is an animal model of neurodevelopmental stress associated with a variety of abnormalities during adulthood. The present study investigated specific behavioral, neurochemical and neurobiological parameters related to dopaminergic and serotonergic function in adult rats subjected to early life MD. Behavioral responses, including the reaction to novelty, the response to d-amphetamine (d-AMP) and the susceptibility to apomorphine (APO) were evaluated in adulthood. Dopamine (DA) and serotonin (5-HT) levels, their metabolites along with their turnover ratios were assessed in distinct rat brain regions. The impact of MD on DARPP-32 protein, D2 and 5-HT2A receptor expression was also estimated in the same brain regions during adulthood. Our results indicated that MD rats were more reactive to novelty behavior and more sensitive to dopaminergic agonists compared to controls. MD rats displayed elevated dopaminergic and serotonergic function in the amygdala and prefrontal cortex, whereas in the striatum only the dopaminergic activity was also increased. Interestingly, MD induced a region-dependent modulation of D2, 5-HT2A receptor and DARPP-32 protein expression. Our findings clearly indicated that early MD stress produces long term behavioral impairments and region-dependent modifications in various neurochemical and neurobiological indices of dopaminergic and serotonergic function in brain regions holding critical roles in the pathophysiology of central nervous system disorders. © 2013. Published by Elsevier B.V

Individual differences in the effects of cannabinoids on motor activity, dopaminergic activity and DARPP-32 phosphorylation in distinct regions of the brain

This study explored the behavioural, neurochemical and molecular effects of 9-tetrahydrocannabinol (9-THC) and WIN55,212-2, in two rat phenotypes, distinguished on the basis of their vertical activity upon exposure to a novel environment, as high responders (HR) and low responders (LR). Motor effects were assessed under habituated vs. non-habituated conditions. Dopaminergic activity and DARPP-32 phosphorylation were measured in the dorsal striatum, nucleus accumbens, prefrontal cortex and amygdala. These cannabinoids influenced motor activity in a biphasic manner, i.e. low doses stimulated, whereas high doses suppressed motor activity. Dopamine (DA) biosynthesis was increased in most brain regions studied following 9-THC administration mainly in HR rats, and low-dose WIN55,212-2 increased DA biosynthesis in HR rats only. Both high and low doses of 9-THC increased DARPP-32 phosphorylation in most brain regions studied in both phenotypes, an effect that was also observed following high-dose WIN55,212-2 administration only in the striatum. The present results provide further support for a key role of cannabinoids in the regulation of motoric responses and elements of dopaminergic neurotransmission and reveal their complex differential effects in distinct rat phenotypes, as seen with other drugs of abuse. Copyright © 2009 CINP