RT Journal Article
SR Electronic
T1 Selective 5-hydroxytryptamine2 antagonists have antidepressant-like effects on differential-reinforcement-of-low-rate 72-second schedule.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 52
OP 59
VO 250
IS 1
A1 G J Marek
A1 A A Li
A1 L S Seiden
YR 1989
UL http://jpet.aspetjournals.org/content/250/1/52.abstract
AB The effects of eleven 5-hydroxytryptamine antagonists with varying selectivity for the 5-hydroxytryptamine2 (5-HT2) relative to the 5-HT1 binding site were assessed in rats responding under a differential-reinforcement-of-low rate 72-sec (DRL 72-s) schedule of reinforcement. Three drugs with a 1000-fold selectivity for the 5-HT2 binding site (ketanserin, ritanserin, pipamperone) increased the reinforcement rate and decreased the response rate similar to antidepressant drugs. The two drugs with roughly the same affinity for both 5-HT1 and 5-HT2 binding sites (methysergide and metergoline) did not increase the reinforcement rate. The maximal increase in the reinforcement rate after 5-HT antagonist administration was positively correlated with the selectivity of the 5-HT antagonists for the 5-HT2 versus the 5-HT1 binding site. The increase in the reinforcement rate after administration of 5-HT antagonists was not correlated with the affinity of the 5-HT antagonists for the alpha-1 adrenergic, alpha-2 adrenergic, histamine-1 or dopamine-2 receptors. The 1000-fold selective 5-HT2 antagonist xylamidine, which does not pass the blood-brain barrier, did not increase the reinforcement rate or decrease the response rate. Thus, selective antagonism of central 5-HT2 relative to 5-HT1 receptors results in antidepressant-like effects on the DRL 72-s schedule. Furthermore, the specificity of the DRL 72-s schedule as a screen for antidepressant drugs was strengthened by the observation that the alpha-1 adrenergic antagonist, prazosin, did not increase the reinforcement rate despite significant decreases in the response rate.