Reductions in binding and functions of D2 dopamine receptors in the rat ventral striatum during amphetamine sensitization

Rats receiving amphetamine (5 mg/kg, i.p. once daily) for 14 continuous days develop behavioral sensitization to a subsequent amphetamine challenge (1 mg/kg) at withdrawal days 8 to 10. The present study was aimed at investigating whether there are changes in binding or functions of striatal D-2 dopamine receptors in amphetamine-sensitized rats. The results indicated that the Bmax value of D-2 receptors in the ventral striatum decreased 40% and 52% 7 and 10 days after amphetamine withdrawal, respectively, without changes in their binding affinities (Kd). During this withdrawal period, the D-2/3 receptor agonist-induced (a) locomotor activation (bromocriptine, 5 mg/kg, i.p. or quinpirole, 1 mg/kg, i.p.) and (b) inhibition of forskolin-enhanced adenylyl cyclase activity (bromocriptine, 50 or 150 mu M) in the ventral striatum were both suppressed as compared with saline controls. The decreases in D-2 receptor function were unrelated to the coupled G-proteins, since none of the G alpha i-3, G alpha o or G alpha q in the ventral striatum exhibited quantitative differences between control and amphetamine sensitized rats. Collectively, these results demonstrate that intermittent amphetamine administration for a period of 14 days leads to diminished D-2 receptor expression and functions in the ventral striatum at late withdrawal periods. The decrease of D-2 receptors might reflect cellular mechanisms underlying the expression of amphetamine sensitization.