Effects of N-methyl-D-aspartate receptor antagonists on reinstatement of cocaine-seeking behavior by priming injections of cocaine or exposures to cocaine-associated cues in rats
Ay. Bespalov et al., Effects of N-methyl-D-aspartate receptor antagonists on reinstatement of cocaine-seeking behavior by priming injections of cocaine or exposures to cocaine-associated cues in rats, BEHAV PHARM, 11(1), 2000, pp. 37-44
The reinstatement of extinguished cocaine self-administration behavior was
studied in rats pretreated with N-methyl-D-aspartate receptor antagonists.
Rats were trained to self-administer intravenous cocaine (0.32 mg/kg/infusi
on) during five consecutive daily sessions that were followed by five conse
cutive daily extinction sessions, during which cocaine was unavailable and
cocaine-associated cues (sound and light) were absent. Neither the competit
ive N-methyl-D-aspartate receptor antagonist D-CPPene (0.3-3 mg/kg) nor the
low-affinity N-methyl-D-aspartate receptor channel blocker memantine (1-10
mg/kg) reinstated extinguished responding. Priming injections of intraveno
us cocaine (Experiment 1), and exposures to cocaine-associated stimuli (buz
zer and light; Experiment 2) engendered responding on the reinforced lever
in excess of that on the non-reinforced lever. In Experiment 1, administrat
ion of D-CPPene or memantine prior to the priming injection of cocaine elim
inated the difference between reinforced-lever and non-reinforced-lever res
ponse rates. For both D-CPPene and memantine, however, this effect was larg
ely due to increased responding upon the non-reinforced lever rather than t
o decreased reinforced-lever responding. In Experiment 2, D-CPPene, but not
memantine, abolished in a dose-dependent manner the selective increase in
reinforced-lever over non-reinforced-lever responding that was induced by e
xposures to cocaine-related stimuli. This effect of D-CPPene was not due to
increased non-reinforced-lever responding. These data help define the boun
daries within which N-methyl-D-aspartate receptor antagonists can prevent r
einstatement of cocaine-seeking behavior (e.g. type of antagonist used and
reinstatement procedure). (C) 2000 Lippincott Williams & Wilkins.