Buspirone, gepirone, ipsapirone, and zalospirone have distinct effects on the differential-reinforcement-of-low-rate 72-s schedule when compared with 5-HTP and diazepam.
The effects of four serotonin (5-HT)-1A compounds (buspirone, gepirone, ipsapirone and zalospirone) were compared with 5-hydroxytryptophan (5-HTP) [a 5-HT precursor with antidepressant (AD) efficacy], and diazepam (a benzodiazepine anxiolytic), on a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule. Past research has shown that AD and anxiolytic compounds each have distinct effects on the DRL 72-s interresponse time (IRT) distribution profile. In the present paper, the profile of the IRT distribution was quantitatively characterized by three metrics: burst ratio, peak location and peak area. 5-HTP shifted the IRT distribution peak toward longer IRT durations, increased reinforcement rate and decreased response rate. The profile of the IRT distribution was not disrupted by 5-HTP. Diazepam disrupted the IRT distribution and increased bursting. In general, the arylpiperazine, 5-HT1A compounds increased reinforcement rate, decreased response rate and disrupted the profile of the IRT distribution. The effects of the four arylpiperazine 5-HT1A compounds on the IRT distribution profile were different from the AD profile of 5-HTP and the benzodiazepine anxiolytic profile of diazepam. Disruption of the IRT distribution by buspirone, gepirone, ipsapirone and zalospirone may result from decreased 5-HT transmission mediated by the presynaptic, somatodendritic 5-HT1A receptor.
University of Chicago, Department of Pharmacological and Physiological Sciences, IL 60637.
J B
JB
Richards
K E
KE
Sabol
T H
TH
Hand
D C
DC
Jolly
G J
GJ
Marek
L S
LS
Seiden
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D018490:Serotonin Agents / Q000494:pharmacology*
D018490:Serotonin Agents; D006916:5-Hydroxytryptophan; D003975:Diazepam