Behavioral effects of a dimethylsulfonium analog of dopamine after injection into the nucleus accumbens and the striatum

Abstract

We have previously synthesized a chemical analog of dopamine (DA) in which the amine group has been replaced by a permanently charged dimethylsulfonium group. In the present study, we have determined whether this compound can exert DA agonist activity in the nucleus accumbens by comparing its effects with those of DA. When DA was injected into the nucleus accumbens of rats pretreated with nialamide, a monoamine oxidase inhibitor, there was marked stimulation of locomotor activity. Similarly, after intraaccumbens injection, the sulfonium analog also produced a marked stimulation of locomotor activity, and this effect was inhibited by the DA receptor antagonist, haloperidol (0.2 mg/kg, IP). However, the sulfonium analog did not stimulate locomotor activity when rats were pretreated with saline instead of nialamide. In addition, the stimulation of locomotor activity produced by the sulfonium analog in rats pretreated with nialamide was completely inhibited by the DA synthesis inhibitor, α-methyl-p-tyrosine. These results suggest that the stimulation of locomotor activity by the sulfonium analog is mediated indirectly through the release of DA. The sulfonium analog was able to produce marked contralateral circling after it was injected into the striatum of rats on the side of the brain in which DA nerve terminals were previously destroyed with 6-hydroxydopamine. Similarly, the sulfonium analog produced a marked stimulation of locomotor activity after it was injected into the nucleus accumbens of rats that were previously injected into this region with 6-hydroxydopamine. These results suggest that the sulfonium analog of dopamine can exert direct as well as indirect DA agonist activity.