Adenosine agonists CGS 21680 and NECA inhibit the initiation of cocaine self-administration.
Administration of the adenosine antagonist caffeine will facilitate the reinstatement of cocaine self-administration responding. This suggests that adenosine receptors may play a role in the motivational systems that regulate cocaine-seeking behaviors. If so then adenosine agonists may act to block cocaine self-administration. To test this hypothesis, the effects of the nonselective adenosine agonist NECA and of the A2A selective agonist, CGS 21680 on the self-administration of cocaine were determined. In these experiments, rats were allowed to obtain intravenous cocaine infusions (0.6 mg/kg/infusion) delivered under a Fixed Ratio 5 schedule. Treatment with either NECA or CGS 21680 in comparison to vehicle administration reduced the number of infusions received per session. This, primarily, was due to a marked increase in the latency for delivery of the first cocaine infusion. Responding after drug-induced delays tended to be at control levels. Adenosine agonists are known to have sedative effects and these actions might play a role in NECA and CGS 21680-induced increases in latencies for cocaine delivery. These results indicate that the administration of adenosine agonists may inhibit cocaine-seeking behaviors. The degree to which these actions are on motivational systems as opposed to involving less specific effects remains to be fully elucidated.
Knapp
C M
CM
Medical Development Research Unit, National Institute on Drug Abuse/Boston Veterans Affairs, MA, USA.
Foye
M M
MM
Cottam
N
N
Ciraulo
D A
DA
Kornetsky
C
C
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016739:Behavior, Addictive / Q000188:drug therapy; D003042:Cocaine / Q000008:administration & dosage*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology* / Q000627:therapeutic use; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012646:Self Administration; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D000959:Antihypertensive Agents; D018765:Dopamine Uptake Inhibitors; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D014665:Vasodilator Agents; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D003042:Cocaine; D000241:Adenosine