Serotonin(2A) receptor modulation of D₁ dopamine receptor-mediated grooming behavior

We have previously observed that intracerebroventricular infusion of a 5-HT(2A) receptor antisense oligonucleotide for 8 days results in an increase in cortical 5-HT(2A) receptor sites and an increase in central 5-HT(2A) receptor function as measured by quantitation of 5-HT(2A) receptor-mediated headshake behavior (28). Because lesioning serotonergic neurons or chronic administration of 5-HT(2A) receptor antagonists does not result in an increase in 5-HT(2A) receptor density or function in the brain, we have taken advantage of this unique upregulation of 5-HT(2A) receptors following 5-HT(2A) receptor antisense oligonucleotide infusion to study the modulation of D₁ receptor-mediated behaviors by 5-HT(2A) receptors. Grooming behavior, elicited by acute injection of SKF 38393, was attenuated after chronic ICV infusion of a 5-HT(2A) receptor antisense oligonucleotide. There was also a reduction in vacuous chewing behavior induced by SKF 38393, which did not reach statistical significance. Other oral behaviors (i.e., tongue protrusions and gnawing at the cage bottom) were not attenuated. An increase in the density of cortical, as well as striatal 5-HT(2A) receptor sites was observed following chronic antisense oligonucleotide administration. There was no change in striatal D₁ dopamine receptors following 5-HT(2A) receptor antisense oligonucleotide administration. SKF 38393-induced grooming behavior was also attenuated in naive rats pretreated acutely with the 5-HT₂ receptor agonist DOI. These results suggest a role for the 5-HT(2A) receptor in the modulation of D₁ receptor function. Copyright (C) 1999 Elsevier Science Inc.