Similar effects of daily cocaine and stress on mesocorticolimbic dopamine neurotransmission in the rat.

Daily exposure to cocaine or stress has been shown to enhance the motor stimulant effect of a subsequent injection of acute cocaine. Considering that both cocaine and stress enhance dopamine neurotransmission in the central nervous system, it was of interest to determine the effects of daily cocaine and stress on the capacity of acute stress to alter dopamine neurotransmission. Rats were injected with cocaine (15 mg/kg, ip) for 3 days or exposed to daily 20 min of footshock stress (0.3 mA/200 msec/sec) for 10 days. Ten to 14 days later, the rats were exposed to acute footshock or sham shock for 0, 5, 10, or 20 min, and the concentration of dopamine and its metabolites was measured in the A10 and A9 dopamine regions, nucleus accumbens, striatum, and prefrontal cortex. It was found that the daily treatments resulted in an enhancement of dopamine metabolism in the prefrontal cortex and nucleus accumbens in response to acute footshock. In contrast, dopamine metabolism was diminished in the A10 region, and no change was measured in the striatum or A9 region. It is proposed that pretreatment with cocaine or stress alters the response of the mesocorticolimbic dopamine neurons to subsequent stress, so that axonal dopamine neurotransmission is enhanced in the terminal fields and somatodendritic dopamine neurotransmission is diminished. Furthermore, the long-lasting influence of daily cocaine and stress on mesocorticolimbic dopamine responsiveness to subsequent stressful experiences may be relevant in the etiology of psychostimulant-induced psychosis.