MOTOR SUPPRESSION AS THE STRESS-INDUCED RESPONSE

Rats and mice exhibited a marked suppression of motility (conditioned suppression; CS) when they were replaced in the same environment in which they had previously received an electric footshock. This CS was considered to be a conditioned emotional response to an environment associated previous with footshock. In the present study, the role played by dopaminergic (DAergic) and opioidergic neuronal systems in the CS was examined. The CS was attenuated by DA receptor agonists such as apomorphine, methamphetamine and SKF 38393 + quinpirole, whereas it was potentiated by the DA receptor antagonist, haloperiodol. Moreover, in a study using in vivo brain microdialysis, a decrease in the striatal DA release in the CS group was observed. The CS was also attenuated by opioid receptor agonists such as morphine and [D-Ala2, Met5]-enkephalinamide (DAMEA), and by the combination of thiorphan and bestatin (an enkephalinase A and an aminopeptidase inhibitor, respectively), which inhibits enkephalin degradation. The effect of these drugs was antagonized not only by the opioid receptor antagonist, naloxone, but also by the DA receptor antagonist, pimozide. The effect of DAMEA on the CS was also counteracted by a low dose of apomorphine which inhibits DA release, and was diminished when DAergic neurons were destroyed by the pretreatment with 6-hydroxydopamine. Furthermore, methionine-enkephalin level and DA turnover in the striatum were decreased in the CS group. These changes in the CS group were reversed by the combination of thiorphan and bestatin. DAMEA also reversed the decrease in the striatal DA turnover in the CS group. These biochemical results consisted with the behavioral effects of DAMEA and the combination of thiorphan and bestatin. The present behavioral and biochemical experiments suggest that the functional reduction in the striatal DAnergic neurons is responsible for the development of stress-induced motor suppression, and that this functional change in the DAergic neurons is regulated by opioidergic neurons.