Withdrawal from chronic administration of cocaine decreases delta opioid receptor signaling and increases anxiety- and depression-like behaviors in the rat

Chronic administration of cocaine has been shown to attenuate the functional capacity of delta opioid receptors to inhibit adenylyl cyclase activity. Abuse and withdrawal from cocaine in humans is associated with increases in anxiety and depression. Since recent research supports the role of delta o...

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Published in:Neuropharmacology Vol. 54; no. 2; pp. 355 - 364
Main Authors: Perrine, Shane A., Sheikh, Imran S., Nwaneshiudu, Chinwe A., Schroeder, Joseph A., Unterwald, Ellen M.
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01.02.2008
Subjects:
Adenylyl cyclase
Adenylyl Cyclases - metabolism
Animals
Anxiety
Anxiety - psychology
Behavior, Animal - drug effects
Benzamides - pharmacology
Cocaine
Cocaine - adverse effects
Data Interpretation, Statistical
Delta opioid receptor
Depression
Depression - psychology
Male
Motor Activity - drug effects
Piperazines - pharmacology
Rat
Rats
Rats, Sprague-Dawley
Receptors, Opioid, delta - agonists
Receptors, Opioid, delta - drug effects
Signal Transduction - drug effects
SNC80
Substance Withdrawal Syndrome - physiopathology
Swimming - psychology
Rat
Adenylyl cyclase
SNC80
Depression
Cocaine
Anxiety
Delta opioid receptor
ISSN:0028-3908, 1873-7064
Online Access:Get full text
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Summary:Chronic administration of cocaine has been shown to attenuate the functional capacity of delta opioid receptors to inhibit adenylyl cyclase activity. Abuse and withdrawal from cocaine in humans is associated with increases in anxiety and depression. Since recent research supports the role of delta opioid receptors in anxiety- and depression-like behaviors in rodents, we hypothesized that functional desensitization of delta opioid receptors contributes to anxiety- and depression-like behavioral phenotypes following short-term withdrawal from chronic administration of cocaine. To test this hypothesis, delta opioid receptor signaling and behaviors were evaluated 24 h after 14 days of binge-pattern cocaine administration (15 mg/kg three times daily at 1 h intervals) in male Sprague–Dawley rats. Results showed that the inhibition of adenylyl cyclase by delta opioid receptor agonists was attenuated in the frontal cortex, nucleus accumbens and caudate putamen 24 h after cessation of cocaine administration. One day withdrawal from chronic administration of cocaine resulted in increased anxiety- and depression-like behaviors as measured by the elevated plus maze and the forced swim test respectively, and no change in locomotor activity. The anxiety- and depression-like behaviors were dose-dependently reduced by acute administration of the selective delta opioid receptor agonist, SNC80. These results demonstrate that early withdrawal from cocaine resulted in increased anxiety and depression, which accompanies the desensitization of delta opioid receptor function. Furthermore, cocaine-induced anxiety- and depression-like behaviors were reversible by the delta opioid receptor agonist SNC80.
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content type line 23
current address: Connecticut College New London, CT
Temple University School of Medicine and The Rockefeller University New York, NY
current address: Wayne State University School of Medicine Detroit, MI
ISSN:0028-3908
1873-7064
DOI:10.1016/j.neuropharm.2007.10.007