High-speed chronoamperometric measurements of mesolimbic and nigrostriatal dopamine release associated with repeated daily stress.

The effects of repeated, once daily exposure to either restraint or tail pinch stress on extracellular levels of dopamine in nucleus accumbens and striatum were electrochemically monitored in conscious rats using high-speed chronoamperometry. Acutely, both tail pinch and restraint increased extracellular dopamine levels in both regions. However, the effect of restraint on mesolimbic and, to some extent, also on nigrostriatal dopamine neurotransmission increased progressively with each daily exposure. While increases in extracellular dopamine elicited by tail pinch varied across test days, no reliable daily enhancement of electrochemical responses to this stress were observed in either of the regions studied. Pretreatment with dopamine autoreceptor-specific doses of apomorphine (50 and 100 micrograms/kg s.c.) potently inhibited stress-elicited responses in nucleus accumbens, indicating that dopamine was the primary electroactive species contributing to the electrochemical signal. The results of this study indicate that the magnitude of stress-elicited increases in levels of extracellular dopamine is determined by the number of previous exposures to stress and are consistent with reports of sensitization to the behavioral effects of stress with repeated testing. The study also provides pharmacological data that are consistent with electrophysiological evidence of increased mesolimbic dopamine cell firing during exposure to stress.