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 expression of immediate early genes, such as c-fos, in the striatum via D1 dopamine receptor activation. This occurs primarily in the striato-nigral neurons. Conversely, neuroleptic drugs, such as haloperidol, which block D2-type dopamine receptors, induce c-fos expression in striatal neurons projecting to the globus pallidus. In order to gain insight into the neurochemical substrates of neuroleptic-induced c-fos expression, we examined the effects of adenosine A2 and N-methyl-D-aspartate (NMDA) receptor antagonists as well as inhibition of nitric oxide synthase, on haloperidol-induced Fos immunoreactivity in the striatum. While blockade of D1 receptors had no effect on haloperidol-induced Fos expression, adenosine A2 receptor antagonists decreased the number of neurons in the striatum expressing haloperidol-induced Fos by half. NMDA receptor antagonists also potently blocked the induction of Fos immunoreactivity by haloperidol, while inhibition of nitric oxide synthase activity had no effect. These results indicate that in the presence of a dopamine D2 antagonist, Fos expression in striato-pallidal neurons is mediated in part through activation of A2 receptors by adenosine, and via NMDA receptor activation by glutamate.
Boegman
R J
RJ
Department of Pharmacology-Toxicology, Queen's University, Kingston, Ontario, Canada.
Vincent
S R
SR
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D017470:Receptors, Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D018047:Receptors, Purinergic P1 / Q000502:physiology*
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D004791:Enzyme Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018047:Receptors, Purinergic P1; D019001:Nitric Oxide Synthase; D006220:Haloperidol