Effects of chronic buspirone treatment on cocaine self-administration.
Cocaine abuse and dependence is a major public health problem that continues to challenge medication-based treatment. Buspirone (Buspar) is a clinically available, non-benzodiazepine anxiolytic medication that acts on both serotonin and dopamine systems. In recent preclinical studies, acute buspirone treatment reduced cocaine self-administration at doses that did not also decrease food-reinforced behavior in rhesus monkeys (Bergman et al, 2012). The present study evaluated the effectiveness of chronic buspirone treatment on self-administration of cocaine and food. Five adult rhesus monkeys (Macaca mulatta) were trained to self-administer cocaine and food during four 1-h daily sessions under a second-order schedule of reinforcement (FR2 [VR 16:S]). Buspirone (0.32 and 0.56 mg/kg/h) was administered intravenously through one lumen of a double-lumen catheter every 20 min for 23 h each day for 7-10 consecutive days. Each buspirone treatment period was followed by saline control treatment until drug- and food-maintained responding returned to baseline levels. Buspirone significantly reduced responding maintained by cocaine, and shifted the dose-effect curve downwards. Buspirone had minimal effects on food-maintained responding. In cocaine discrimination studies, buspirone (0.1-0.32 mg/kg, IM) did not antagonize the discriminative stimulus and rate-altering effects of cocaine in four of six monkeys. These findings indicate that buspirone selectively attenuates the reinforcing effects of cocaine in a nonhuman primate model of cocaine self-administration, and has variable effects on cocaine discrimination.
Alcohol and Drug Abuse Research Center, Harvard Medical School-McLean Hospital, Belmont, MA 02478, USA. nmello@mclean.harvard.edu
Nancy K
NK
Mello
Peter A
PA
Fivel
Stephen J
SJ
Kohut
Jack
J
Bergman
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D016739:Behavior, Addictive / Q000517:prevention & control* / Q000523:psychology; D002065:Buspirone / Q000008:administration & dosage*; D003042:Cocaine / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D004435:Eating / Q000187:drug effects* / Q000502:physiology / Q000523:psychology; D008253:Macaca mulatta; D008297:Male; D012646:Self Administration; D016896:Treatment Outcome
D014151:Anti-Anxiety Agents; D003042:Cocaine; D002065:Buspirone