Nucleus accumbens as a substrate for the aversive stimulus effects of opiate withdrawal.
Previous studies from our laboratory using methylnaloxonium, a hydrophilic antagonist, showed that opiate receptors in the region of the nucleus accumbens are important for the acute reinforcing effects of heroin in non-dependent rats. A similar increased sensitivity to the response disruptive effects of intracerebrally injected methylnaloxonium in opiate dependent rats was observed in a fixed-ratio (FR) baseline of operant behaviors. These results suggest that the same opiate receptors in the region of the nucleus accumbens important for the positive reinforcing stimulus properties of opiates may also be responsible for the response disruptive, aversive stimulus properties of opiate withdrawal. These results also suggest that the neural substrates of some aspects of dependence may be partly related to those of the reinforcing effects of opiates. In particular, it is hypothesized that "euphoria" and "dysphoria" induced by opiates may reflect opponent motivational processes operating at a cellular level within the nucleus accumbens.
Koob
G F
GF
Department of Basic and Clinical Research, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Wall
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TL
Bloom
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FE
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009270:Naloxone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000502:physiology*; D000644:Quaternary Ammonium Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012686:Septal Nuclei / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013997:Time Factors
D000644:Quaternary Ammonium Compounds; D009270:Naloxone; C041269:N-methylnaloxone; D009020:Morphine