Preference for a cocaine-associated environment is attenuated by augmented accumbal serotonin in cocaine withdrawn rats.
BACKGROUND
Recent studies have found decreased serotonin (5-HT) transmission within the nucleus accumbens following withdrawal from chronic cocaine.


OBJECTIVE
We sought to investigate whether increasing brain 5-HT levels would decrease behavioral responses that occur following cocaine withdrawal, namely increased preference for a cocaine environment and anxiety.


METHODS
The conditioned place preference and the defensive burying paradigms were used to measure the behavioral responses that occur 1 week following cocaine withdrawal.


RESULTS
We show that pharmacological agents that increase 5-HT transmission (sertraline or 5-hydoxytryptophan, 5-HTP) abolish the preference of subchronically cocaine-treated, abstinent rats for a cocaine-associated environment. Similar results were seen when sertraline was microinjected into the nucleus accumbens. Conversely, rats acutely conditioned with cocaine showed an increased preference for a cocaine-associated environment when pretreated with these drugs. Sertraline also decreased the heightened anxiety-like behaviors found in subchronically treated cocaine rats.


CONCLUSIONS
These results indicate that drugs that augment 5-HT function may reduce the desire for cocaine following cocaine withdrawal, and thus facilitate cocaine abstinence in dependent subjects.
Harris
G C
GC
Department of Psychiatry, University of Pennsylvania, VAMC, Philadelphia 19104, USA.
Altomare
K
K
Aston-Jones
G
G
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004777:Environment; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000096:biosynthesis*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D018765:Dopamine Uptake Inhibitors; D012701:Serotonin; D006916:5-Hydroxytryptophan; D003042:Cocaine