Self-administration of morphine, DAMGO, and DPDPE into the ventral tegmental area of rats.
Intracranial self-administration of mu- and delta-opioid agonists was demonstrated in male Long-Evans rats. Independent groups were allowed to lever-press for ventral tegmental area (VTA) microinfusions of morphine, the selective mu agonist [D-Ala2,N-Me-Phe4-Gly5-ol]-enkephalin (DAMGO), the selective delta-agonist [D-Pen2,D-Pen5]-enkephalin (DPDPE), or ineffective drug vehicle. Morphine, DAMGO, and DPDPE were each effective in establishing and maintaining lever-pressing habits. Lever-pressing responses were extinguished during a session when vehicle was substituted for drug, and reinstated when drug reinforcement was reestablished. Thus, it appears that VTA mu- and delta-opioid receptors are each involved in reinforcement of opiate self-administration. The effective dose of DAMGO--both for establishing and for maintaining the lever-press habit--was 100 times lower than the effective doses for DPDPE and morphine, suggesting that the major contribution of VTA mechanisms to intravenous heroin self-administration involves an action on mu-opioid receptors.
Devine
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DP
Department of Psychology, Concordia University, Montreal, Quebec, Canada.
Wise
R A
RA
D000700:Analgesics / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000008:administration & dosage* / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017465:Receptors, Opioid, delta / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000502:physiology; D012054:Reinforcement, Psychology; D012646:Self Administration; D013239:Stereotyped Behavior / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
D000700:Analgesics; D004745:Enkephalins; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-