Dopaminergic mechanism for caffeine-produced cocaine seeking in rats.
Systemic administration of caffeine reinstates extinguished cocaine self-administration behavior in rats, but the mechanism mediating this behavioral effect has not been established. The present study examined the role of adenosinergic A2 and dopaminergic mechanisms in caffeine-produced cocaine seeking. Following extinction of cocaine self-administration, experimenter-administered injections of caffeine (1.25-20 mg/kg) and theophylline (1-10 mg/kg) dose-dependently reinstated extinguished cocaine-seeking behavior. Administration of the adenosinergic A2 antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX; 0.546-2.18 microg/kg), failed to produce cocaine seeking. Pretreatment with doses of the adenosine A1/A2 agonist 5'-N-ethylcarboxamidoadenosine (NECA; 0.003-0.03 mg/kg) that were below those that produced marked sedation failed to block reinstatement. These data suggest that methylxanthine-produced cocaine seeking is not due to adenosine A2 receptor antagonism. In contrast, pretreatment with the dopaminergic D1-like antagonist SCH 23390 (0.005-0.02 mg/kg) or the D2-like antagonist eticlopride (0.03-0.3 mg/kg) produced a dose-dependent attenuation of caffeine-produced reinstatement at doses that did not decrease cocaine self-administration. These findings suggest that dopaminergic mechanisms underlie the ability of caffeine to reinstate extinguished cocaine-taking behavior.
Green
Thomas A
TA
Department of Psychology, Texas A&M University, College Station, TX, USA.
Schenk
Susan
S
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000502:physiology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012457:Salicylamides / Q000494:pharmacology; D012646:Self Administration; D013806:Theophylline / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001552:Benzazepines; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D058915:Purinergic P1 Receptor Antagonists; D012457:Salicylamides; D014665:Vasodilator Agents; D019830:Adenosine-5'-(N-ethylcarboxamide); D002110:Caffeine; D013806:Theophylline; C045989:eticlopride; D000241:Adenosine; D004298:Dopamine