title: Effect of time-out duration on the reinforcing strength of cocaine assessed under a progressive-ratio schedule in rhesus monkeys.
abstract: Progressive-ratio (PR) schedules of reinforcement have provided valuable information regarding the reinforcing strength of cocaine and the underlying neurobiological mechanisms. Parametric manipulations, such as altering time-out (TO) values, can affect the shape of the cocaine dose-response curve. Earlier studies have used PR schedules with widely varying parameters, thus complicating comparisons across experiments. This study evaluated the reinforcing strength of cocaine (0.005-0.9 mg/kg) as a function of post-reinforcement TO duration (5, 10, 30, or 60 min) under a PR schedule in rhesus monkeys. Daily sessions ended when 2 h elapsed without an injection; the breakpoint value was defined as the total number of injections. When the TO was 10 min, the relationship between cocaine dose and the number of injections received (i.e. BP) was characterized by an inverted U-shaped curve in all monkeys. Increasing the TO to 30 min resulted in a rightward shift of the ascending limb of the dose-response curve, but did not affect self-administration of higher doses. The number of injections received of a low cocaine dose was not further increased when the TO was shortened to 5 min, nor did increasing the TO to 60 min alter self-administration of the highest tested dose. These results suggest that drug accumulation plays a role in determining the reinforcing strength of low and intermediate cocaine doses under PR schedules. However, the reinforcing strength of higher cocaine doses was unaffected by manipulating TO, suggesting that the BP value is a useful measure of reinforcing strength.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martelle
authors.forename: Paul W
authors.initials: PW
authors.lastname: Czoty
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nader
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D009042:Motivation; D012055:Reinforcement Schedule; D012646:Self Administration
chemical_list: D018765:Dopamine Uptake Inhibitors; D003042:Cocaine
references.citation: J Pharmacol Exp Ther. 1982 May;221(2):384-93
references.pmid: 7077533
references.citation: Behav Pharmacol. 1990;1(4):283-301
references.pmid: 11175414
references.citation: J Pharmacol Exp Ther. 1991 Apr;257(1):247-61
references.pmid: 2019989
references.citation: J Pharmacol Exp Ther. 2007 May;321(2):573-82
references.pmid: 17272677
references.citation: Drug Alcohol Depend. 2006 Dec 1;85(3):213-20
references.pmid: 16730922
references.citation: Psychopharmacology (Berl). 2003 May;167(3):324-32
references.pmid: 12652348
references.citation: Psychopharmacologia. 1975 Jul 23;43(1):81-3
references.pmid: 1161995
references.citation: J Neurosci Methods. 1996 May;66(1):1-11
references.pmid: 8794935
references.citation: Psychopharmacology (Berl). 1995 Aug;120(3):296-302
references.pmid: 8524977
references.citation: Pharmacol Biochem Behav. 1997 Jul;57(3):441-7
references.pmid: 9218268
references.citation: J Pharmacol Exp Ther. 2002 Nov;303(2):640-8
references.pmid: 12388646
references.citation: Pharmacol Biochem Behav. 1973 Jan-Feb;1(1):67-71
references.pmid: 4204513
references.citation: Psychopharmacology (Berl). 1996 Jun;125(4):361-70
references.pmid: 8826541
references.citation: J Pharmacol Exp Ther. 2002 Oct;303(1):211-7
references.pmid: 12235253
references.citation: Psychopharmacology (Berl). 2002 Oct;164(1):19-26
references.pmid: 12373415
references.citation: J Pharmacol Exp Ther. 2003 Oct;307(1):356-66
references.pmid: 12954808
references.citation: Psychopharmacology (Berl). 1998 Oct;139(3):169-84
references.pmid: 9784071