Chronic stress changes prepulse inhibition after amphetamine challenge: the role of the dopaminergic system

The goal of this research was to examine the influence of chronic mild stress (CMS) on prepulse inhibition (PPI). We used an amphetamine challenge to study the role of the dopaminergic system in limbic structures. Chronic stress caused a reduction in both sucrose preference and body weight. It was found that the initially strong response to amphetamine in the control rats was weakened after stress on both the behavioural and biochemical levels: improved PPI, decreased dopamine D2 receptor expression in the central nucleus of amygdala (CeA) and nucleus accumbens (NAC), and decreased dopamine and 3-MT (3-methoxytyramine) levels in NAC. We observed that the stress-evoked attenuation of amphetamine-induced stimulation was also paralleled by changes in corticosterone level. These effects were accompanied by a decrease in both glutamate and the glutamate/gamma-aminobutric acid (GABA) ratio in the NAC. The interpretation of these results is that prolonged stress induces compensatory mechanisms in the mesolimbic system which are responsible for psychostimulant (amphetamine) effects.