Changes in response to a dopamine receptor antagonist in rats with escalating cocaine intake.
Psychopharmacology. 2004-04-01; 172(4): 450-454
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1. Psychopharmacology (Berl). 2004 Apr;172(4):450-4. Epub 2003 Nov 28.
Changes in response to a dopamine receptor antagonist in rats with escalating
Ahmed SH(1), Koob GF.
(1)Laboratoire de Neuropsychobiologie Desadaptations, Centre National de la
Recherche Scientifique, Unite Mixte de Recherche 5541, Universite Victor Segalen
Bordeaux 2, Bordeaux, France.
RATIONALE AND OBJECTIVES: Prolonged access to cocaine self-administration (long
access or LgA) produces an escalation in drug intake not observed with limited
access to the drug (short access or ShA). The present study tested the hypothesis
that escalating use of cocaine is associated with chronic alterations in dopamine
METHODS: After escalation of cocaine self-administration, ShA and LgA rats were
challenged with different subcutaneous doses of cis-flupenthixol (10-270 micro
g/kg), a highly selective dopamine receptor antagonist.
RESULTS: In both groups, increasing doses of cis-flupenthixol first produced an
increase in the number of cocaine injections and then a dramatic suppression of
behavior. This biphasic dose-effect function-which replicates previous findings
from this laboratory-was shifted to the left in LgA rats relative to ShA rats,
thereby decreasing the threshold dose at which behavior was completely
CONCLUSIONS: These data support the hypothesis that alterations in dopamine
neurotransmission contribute to escalation of cocaine self-administration.
PMID: 14647962 [Indexed for MEDLINE]