Effects of chronic stress on methamphetamine-induced dopamine depletions in the striatum

Research has shown that exposure to repeated stress alters acute behavioral and neurochemical responses to drugs of abuse. However, few studies have characterized the longer-term detrimental effects of psychostimulant drugs such as methamphetamine (METH) after exposure to chronic stress. The current study tested whether 10 days of unpredictable stress produced greater striatal dopamine depletions after neurotoxic injections of METH and whether monoamine reuptake blockers protected against stress/METH-induced DA depletion. Male rats were exposed to 10 d of unpredictable stress or weighed daily but not stressed. On day 11, all rats were given 4 injections of 0, 7.5, or 10 mg/kg METH, 1 injection every 2 h, and tissue collected 7 d later. Male rats exposed to unpredictable stress had greater depletions of striatal dopamine tissue content than nonstressed controls injected with METH. In a separate study, rats were treated with vehicle, desipramine (10 mg/kg), or fluoxetine (5 mg/kg) daily during the 10-d stress regimen. These antidepressants did not attenuate the stress-potentiated depletion of striatal dopamine. These findings suggest that chronic unpredictable stress enhances vulnerability of the brain to neurotoxic effects of psychostimulants, but this vulnerability is mediated through mechanisms other than the norepinephrine or serotonin uptake systems.