Involvement of adenylate cyclase inhibition in dopamine autoreceptor regulation of tyrosine hydroxylase in rat nucleus accumbens.

In homogenates of rat nucleus accumbens, quinpirole, a dopamine (DA) D2 receptor agonist, inhibited the activation of tyrosine hydroxylase (TH) elicited by either forskolin, an activator of adenylate cyclase, or rolipram, a cyclic nucleotide phosphodiesterase inhibitor. The inhibition produced by 1 microM quinpirole was completely antagonized by the D2 blocker L-sulpiride (2 microM). Quinpirole failed to inhibit the stimulation of TH elicited by dibutyryl cyclic AMP (2 mM), which acts independently of adenylate cyclase. Quinpirole (10 microM) significantly inhibited the stimulation of adenylate cyclase activity elicited by 1 microM forskolin. These results indicate that mesolimbic DA autoreceptors can regulate TH activity by inhibiting a presynaptic adenylate cyclase system.