Serotonin2A receptor modulation of D1 dopamine receptor-mediated grooming behavior

We have previously observed that intracerebroventricular infusion of a 5-HT2A receptor antisense oligonucleotide for 8 days results in an increase in cortical 5-HT2A receptor sites and an increase in central 5-HT2A receptor function as measured by quantitation of 5-HT2A receptor-mediated headshake behavior (28). Because lesioning serotonergic neurons or chronic administration of 5-HT2A receptor antagonists does not result in an increase in 5-HT2A receptor density or function in the brain, we have taken advantage of this unique upregulation of 5-HT2A receptors following 5-HT2A receptor antisense oligonucleotide infusion to study the modulation of D1 receptor-mediated behaviors by 5-HT2A receptors. Grooming behavior, elicited by acute injection of SKF 38393, was attenuated after chronic ICV infusion of a 5-HT2A 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-HT2A receptor sites was observed following chronic antisense oligonucleotide administration. There was no change in striatal D1 dopamine receptors following 5-HT2A 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-HT2A receptor in the modulation of D1 receptor function.