INVOLVEMENT OF ADENOSINE AND GLUTAMATE RECEPTORS IN THE INDUCTION OF C-FOS IN THE STRIATUM BY HALOPERIDOL

The psychostimulant drugs amphetamine and cocaine induce the expressio n of immediate early genes, such as c-fos, in the striatum via D-1 dop amine receptor activation. This occurs primarily in the striato-nigral neurons. Conversely, neuroleptic drugs, such as haloperidol, which bl ock D-2-type dopamine receptors, induce c-fos expression in striatal n eurons projecting to the globus pallidus. In order to gain insight int o the neurochemical substrates of neuroleptic-induced c-fos expression , we examined the effects of adenosine A(2) and N-methyl-D-aspartate ( NMDA) receptor antagonists as well as inhibition of nitric oxide synth ase, on haloperidol-induced Fos immunoreactivity in the striatum. Whil e blockade of D-1 receptors had no effect on haloperidol-induced Fos e xpression, adenosine A(2) receptor antagonists decreased the number of neurons in the striatum expressing haloperidol-induced Fos by half. N MDA receptor antagonists also potently blocked the induction of Fos im munoreactivity by haloperidol, while inhibition of nitric oxide syntha se activity had no effect. These results indicate that in the presence of a dopamine D-2 antagonist, Fos expression in striato-pallidal neur ons is mediated in part through activation of A(2) receptors by adenos ine, and via NMDA receptor activation by glutamate. (C) 1996 Wiley-Lis s, Inc.