Genotype-dependent effects of chronic stress on apomorphine-induced alterations of striatal and mesolimbic dopamine metabolism

After 10 daily consecutive restraint experiences, DBA/2 (DBA) mice showed an increase of climbing behavior after injection of 0.25 mg/kg of the dopamine (DA) agonist apomorphine (APO), while no changes were observed following vehicle or 1 mg/kg of APO. By contrast, chronically stressed C57BL/6 (C57) mice showed a clear-cut decrease of climbing behavior at the dose of 0.25 mg/kg of APO and a similar, although less pronounced, effect of stress on the behavior of mice injected either with vehicle or with 1 mg/kg APO. The DA agonist at these same doses decreased 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT) concentrations in the caudatus putamen (CP) and nucleus accumbens septi (NAS) of both strains. Higher DOPAC, HVA and 3-MT concentrations were evident in stressed DBA mice receiving 0.25 mg/kg but not 1 mg/kg of APO, in both CP and NAS. Concerning C57 mice, lower concentrations of the 3 metabolites were present at both doses of APO in the NAS of stressed mice in comparison with non-stressed animals, while no significant stress-related effects were evident in the CP. Non-significant differences between control and stressed mice of both strains were evident as regards DA concentrations in CP and NAS. These results suggest that repeated stressful experiences lead to a hyposensitivity of DA presynaptic receptors in DBA mice while they produce a sensitization of mesolimbic DA presynaptic receptors possibly accompanied by down-regulation of postsynaptic DA receptors in the C57 strain.