Effects of SCH 23390 and eticlopride on cocaine-seeking produced by cocaine and WIN 35,428 in rats.
BACKGROUND
Exposure to a small amount of cocaine can trigger relapse, and so an understanding of the mechanisms underlying cocaine-seeking are important for the development of effective anti-relapse treatments.


OBJECTIVE
The present study sought to compare the contributions of dopamine D(1)- and D(2)-like receptors in drug-seeking produced by cocaine and WIN 35,428.


METHODS
Reinstatement of extinguished cocaine self-administration was measured for rats that received injections of cocaine (5.0-20.0 mg/kg) or WIN 35,428 (0.1-1.0 mg/kg) following extinction. Prior to the injection of cocaine or WIN 35,428, rats received an injection of the D(1)-like antagonist, SCH 23390 (0.001-0.010 mg/kg) or the D(2)-like antagonist, eticlopride (0.01-0.30 mg/kg). Effects of SCH 23390 (0.01 mg/kg) on cocaine-produced locomotor activation were also measured in separate groups of rats.


RESULTS
The ability of both cocaine and WIN 35,428 to produce cocaine-seeking was dose-dependent. Within the range of doses tested, SCH 23390 failed significantly to attenuate the ability of either cocaine or WIN 35,428 to reinstate extinguished cocaine self-administration, although cocaine-produced locomotor activation was significantly attenuated by pretreatment with the highest dose of SCH 23390. Eticlopride attenuated both cocaine and WIN 35,428 produced cocaine-seeking but lower doses were required to decrease WIN 35,428-produced cocaine-seeking.


CONCLUSIONS
These results suggest that dopamine D(2) mechanisms are involved in cocaine-seeking produced by both cocaine and WIN 35,428. The lower potency of eticlopride in attenuating cocaine-produced cocaine-seeking suggest that cocaine's effects at sites other than the dopamine transporter contribute to its ability to elicit drug-seeking.
Schenk
Susan
S
School of Psychology, Victoria University of Wellington, P.O. Box 600, Wellington, New Zealand, New Zealand. susan.schenk@vuw.ac.nz.
Gittings
Dave
D
School of Psychology, Victoria University of Wellington, P.O. Box 600, Wellington, New Zealand, New Zealand.
D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced / Q000188:drug therapy; D001552:Benzazepines / Q000494:pharmacology* / Q000627:therapeutic use; D003042:Cocaine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D012457:Salicylamides / Q000494:pharmacology* / Q000627:therapeutic use
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine; C045989:eticlopride