Modulation of rat neocortical high-voltage spindle activity by 5-HT1/5-HT2 receptor subtype specific drugs.
To investigate the role of serotonin (5-hydroxytryptamine; 5-HT) receptors in the modulation of rat thalamocortical oscillations, we studied the effects of 5-HT1/5-HT2 receptor subtype specific drugs on neocortical high-voltage spindle activity in adult male rats. A 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.03, 0.1, 0.3 and 1.0 mg/kg s.c.), had no effect on neocortical high-voltage spindle activity. Furthermore, a mixed 5-HT1/5-HT2 receptor antagonist, methysergide (1.0, 5.0 and 15.0 mg/kg i.p.), had no effect, whereas a non-specific mixed 5-HT1/5-HT2 receptor antagonist, methiothepin (0.2, 1.0 and 5.0 mg/kg i.p.), significantly increased neocortical high-voltage spindles. Of the 5-HT2 receptor antagonists, ritanserin (0.1, 1.0 and 5.0 mg/kg s.c.) had no effect, whereas ketanserin (1.0, 5.0 and 20.0 mg/kg s.c.) increased neocortical high-voltage spindles, but only at the highest dose used. A 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.5, 1.0 and 2.0 mg/kg s.c.), at the two highest doses significantly decreased neocortical high-voltage spindle activity, and this effect was blocked by the 5-HT2 receptor antagonists, ketanserin (1.0, 5.0 and 20.0 mg/kg s.c.) and ritanserin (1.0 and 5.0 mg/kg s.c.), as well as by methiothepin (0.2, 1.0 and 5.0 mg/kg i.p.) and methysergide (1.0, 5.0 and 15.0 mg/kg i.p.). Furthermore, unilateral intrathalamic infusions, but not intrahippocampal control infusions, of DOI (10 and 50 micrograms/1.0 microliters/rat) decreased neocortical high-voltage spindle activity and systemic administration of ketanserin (20.0 mg/kg s.c.) completely blocked this effect. The present results suggest that (1) the serotonergic system modulates rat thalamocortical oscillations as measured by neocortical high-voltage spindle activity, (2) activation of 5-HT2 receptors, possibly located in the thalamus, with a specific 5-HT2 receptor agonist, DOI, causes a reduction in rat neocortical high-voltage spindle activity.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D004569:Electroencephalography / Q000187:drug effects*; D007263:Infusions, Parenteral; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D016713:Ritanserin / Q000494:pharmacology; D013788:Thalamus / Q000187:drug effects*
D000662:Amphetamines; D011985:Receptors, Serotonin; D016713:Ritanserin; D008719:Methiothepin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D008784:Methysergide