Journal
NEUROPSYCHOPHARMACOLOGY
Volume 34, Issue 4, Pages 874-886Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2008.111
Keywords
morphine; mu-opioid receptor; opiate; sensitization; cross-sensitization; ventral pallidum
Categories
Funding
- Loyola University Chicago Graduate School
- United States Public Health [DA05255, DA019783]
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Repeated, intermittent exposure to drugs of abuse results in response enhancements to subsequent drug treatments, a phenomenon referred to as sensitization. As persistent neuronal sensitization may contribute to the long-lasting consequences of drug abuse, characterizing the neuroanatomical substrates of sensitization is providing insights into addiction. It is known that the ventral tegmental area (VTA) is necessary for induction, and expression involves the nucleus accumbens (NAc). We reveal here that the ventral pallidum (VP), a brain region reciprocally innervated by the VTA and the NAc, is a critical mediator of opiate-induced behavioral sensitization. Blockade of VP mu-opioid receptors (via intra-VP CTOP injections) negated the ability of systemic administration of the opiate, morphine to induce motor sensitization, and for sensitized rats to subsequently express enhanced responding to a morphine challenge. Intra-VP morphine was sufficient to induce motor sensitization, and this sensitization was expressed following 17 days of withdrawal. Rats with a treatment history of intra-VP morphine demonstrated cross-sensitization to a challenge injection of systemically administered morphine. Conversely, repeated systemic treatments of morphine cross-sensitized to an intra-VP morphine challenge. These results indicate that activation of VP mu-opioid receptors is sufficient to evoke behavioral sensitization and that these receptors are necessary for sensitized responding to systemic morphine. The study pioneers the concept that both development and expression of drug-induced sensitization are regulated by the VP. Thus, the VP is likely an important contributor to neuronal adaptations that underlie addiction.
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