Dopamine release during cocaine self-administration in rats: effect of SCH23390

This experiment tested the hypotheses that: (1) self-administration of cocaine would produce an increase in dopamine (DA) oxidation current in the nucleus accumbens (n. acc.); and (2) a faster rate of cocaine intake in the presence of a D₁ receptor antagonist would produce a greater increase in DA levels. Rats trained to self-administer cocaine under a fixed-ratio 2 schedule were implanted with stearate-modified graphite paste electrodes bilaterally in the n. acc. The effect of pretreatment with the D₁ receptor antagonist, SCH23390, on the DA oxidation current associated with self-administration of cocaine (1 mg/inj.) or saline was investigated using chronoamperometry. Pretreatment with SCH23390 produced a 2-fold increase in the amount of cocaine intake. This in turn resulted in a 2-fold increase in the DA oxidation current recorded in the n. acc. Pretreatment with SCH23390 did not, however, produce any significant change in either the number of saline injections received or the DA oxidation current recorded during saline self-administration. These findings show that cocaine increases DA oxidation currents in the n. acc., and that both the rate of cocaine self-administration and the magnitude of these currents increase even further following SCH23390. The results also imply that the baseline rate of cocaine self-administration does not result in the occupation of all possible DA transporter sites.