CONTRIBUTION OF BLOCKADE OF THE NORADRENALINE CARRIER TO THE INCREASEOF EXTRACELLULAR DOPAMINE IN THE RAT PREFRONTAL CORTEX BY AMPHETAMINEAND COCAINE

This study was performed to investigate the relative role of noradrena line (NA) and dopamine (DA) carrier blockade in the effects of psychos timulants on DA transmission in the rat prefrontal cortex (PFCX). To t his end, changes of extracellular DA and NA in the PFCX and of extrace llular DA in the nucleus accumbens (NAc) were measured following the a dministration of amphetamine and cocaine, which are known to bind to b oth DA and NA carriers, or GBR 12909, a selective DA carrier blocker. After non-intravenous injection, amphetamine (0.25 and 0.5 mg/kg, s.c. ) and cocaine (5 and 10 mg/kg, i.p.) increased extracellular DA in the PFCX to a larger extent than in the NAc, while the reverse applied to GBR 12909 (2.5 and 5 mg/kg, i.p.). These differences were obtained in spite of the fact that the three drugs elicited at each dose level a similar peak increase of extracellular DA in the NAc. Amphetamine and cocaine also increased extracellular NA in the PFCX and this effect wa s quantitatively similar to that on extracellular DA in the same area. Intravenous doses of cocaine and GBR 12909, corresponding to those wh ich maintain self-administration in the rat, while equieffective in ra ising extracellular DA in the NAc, had different effects on extracellu lar DA in the PFCX. In fact, in contrast to cocaine, GBR 12909 increas ed extracellular DA in the PFCX to a lesser extent than in the NAc or did not modify it at all. The peak increase of extracellular DA in the PFCX was highly correlated to that of NA in the same area but was poo rly correlated to the increase of extracellular DA in the NAc. These r esults suggest that amphetamine and cocaine increase extracellular DA in the PFCX largely through the blockade of the NA carrier. Direct evi dence for this hypothesis was provided by the observation that, when t he NA carrier was blocked by reverse dialysis of the PFCX with desipra mine (1 mu M), cocaine and GBR 12909 lost their differences in the abi lity to increase extracellular DA in the PFCX.