Augmented accumbal serotonin levels decrease the preference for a morphine associated environment during withdrawal.
Recent studies have found that acute morphine administration increases serotonin (5-HT) transmission within the nucleus accumbens and other forebrain regions. In contrast, 5-HT transmission is depressed during withdrawal from chronic morphine. We show that pharmacological agents that increase brain 5-HT levels (fluoxetine or 5-hydoxytryptophan, 5-HTP) abolish the preference of chronically morphine-treated, withdrawn rats for a morphine-associated environment. Similar results were seen when fluoxetine was microinjected into the nucleus accumbens. Conversely, rats given morphine acutely showed an enhanced preference for a morphine-associated environment when pretreated with these agents. Fluoxetine also decreased the heightened anxiety found in morphine withdrawn rats. The results of our study indicate that drugs that augment 5-HT levels may reduce the desire for morphine during withdrawal.
Harris
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GC
University of Pennsylvania, VAMC 151 Rm A520, University and Woodland Ave, Philadephia, PA 19104, USA.
Aston-Jones
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G
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D004780:Environment, Controlled; D005473:Fluoxetine / Q000494:pharmacology; D019416:Head Movements / Q000187:drug effects / Q000502:physiology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
D005473:Fluoxetine; D012701:Serotonin; D009020:Morphine; D006916:5-Hydroxytryptophan