The effects of SB 224289 on anxiety and cocaine-related behaviors in a novel object task.
Cocaine facilitates dopamine transmission from ventral tegmental area (VTA) neurons that project to nucleus accumbens (NAcc), and previous experiments suggest that serotonin-1B (5-HT1B) receptors are involved in this effect. Specifically, activation of 5-HT1B receptors in VTA during cocaine exposure increases dopamine release in NAcc and enhances cocaine-induced locomotor activity, reward, and reinforcement. Thus, it is reasonable to hypothesize that blocking 5-HT1B activity may have the opposite effect. To investigate this hypothesis, SB 224289, a highly selective 5-HT1B antagonist, was used to block this receptor. In an open field/novel object exploration test, SB 224289 reduced cocaine-induced locomotion. However, SB 224289 also increased anxiety-like behavior, both alone and in combination with cocaine. This experiment gives evidence that 5-HT1B antagonists may reduce some of the behavioral effects of cocaine, but may have negative effects on anxiety as well.
Hoplight
B J
BJ
1-University of Washington, Box 359911, Harborview Medical Center, 325-9th Ave., Seattle, WA 98104, USA.
Vincow
E S
ES
Neumaier
J F
JF
D000818:Animals; D001007:Anxiety / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004777:Environment; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010881:Piperidones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology*; D013268:Stimulation, Chemical
D010881:Piperidones; D044302:Receptor, Serotonin, 5-HT1B; C108518:SB 22489G; D012702:Serotonin Antagonists; D013141:Spiro Compounds; D003042:Cocaine