Document Detail

Evidence for N-methyl-D-aspartate receptor mediation of cocaine induced corticosterone release and cocaine conditioned stimulant effects.
MedLine Citation:
PMID:  7654307     Owner:  NLM     Status:  MEDLINE    
The role of the N-methyl-D-aspartate (NMDA) receptors in cocaine conditioning and sensitization of locomotor activity was studied in four groups of Sprague-Dawley rats. A sub-motoric dose of the NMDA antagonist MK-801 (0.1 mg/kg, i.p.) was employed using a novel dual-compartment Pavlovian drug conditioning paradigm. The animals were placed sequentially in two different test environments in which locomotor activity was monitored. In the first compartment, the animals always received a non-drug test for 20 min. Upon completion of this test, the animals received either saline, cocaine (10 mg/kg i.p.), MK-801 or MK-801 plus cocaine depending on group assignment and were then placed immediately into the second compartment and again tested for 20 min. A total of six non-drug and six drug tests were conducted every other day over a 12-day period. Across all drug/saline treatment and post-treatment tests for conditioning, there were no statistical differences in locomotor activity among the saline and drug treatment groups in the non-drug test environment. In the drug/saline associated environment, however, cocaine had a reliable stimulant effect on locomotion when administered alone or in combination with MK-801. Following a 1-day and again after 21-days of withdrawal, all animals were administered a non-drug test for conditioning in which no injections were administered. On both tests, all groups had equivalent activity levels in the non-drug environment. In the drug/saline environment, only the cocaine group of the three drug treatment groups exhibited conditioned hyperlocomotion. Importantly, MK-801 blocked conditioned hyperlocomotion in the combined cocaine+MK-801 group. MK-801 did not alter serum or brain cocaine concentration or the cocaine effects on dopamine metabolism in limbic brain tissue. The co-administration of MK-801 with cocaine, however, blocked the corticosterone release effect of cocaine. Thus, the NMDA receptor site appears critical for cocaine induced conditioning and for corticosterone release.
E N Damianopoulos; R J Carey
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Behavioural brain research     Volume:  68     ISSN:  0166-4328     ISO Abbreviation:  Behav. Brain Res.     Publication Date:  1995 Jun 
Date Detail:
Created Date:  1995-10-05     Completed Date:  1995-10-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8004872     Medline TA:  Behav Brain Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  219-28     Citation Subset:  IM    
SUNY Health Science Center, Syracuse, USA.
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MeSH Terms
Arousal / drug effects*
Association Learning / drug effects
Brain / drug effects
Cocaine / antagonists & inhibitors,  pharmacology*
Conditioning, Classical / drug effects*
Corticosterone / blood*
Dizocilpine Maleate / pharmacology
Injections, Intraperitoneal
Motor Activity / drug effects
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate / drug effects*
Social Environment
Grant Support
Reg. No./Substance:
0/Receptors, N-Methyl-D-Aspartate; 50-22-6/Corticosterone; 50-36-2/Cocaine; 77086-22-7/Dizocilpine Maleate

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