Document Detail

Irt>t schedule controlled behavior in 'learned-helpless' rats: effects from a cannabinoid agonist.
MedLine Citation:
PMID:  16753187     Owner:  NLM     Status:  MEDLINE    
Human depression is partly a congenital disorder. Aspects of the behavior accompanying depression can be magnified by genetic manipulation of bred animal species. Learned Helplessness (LH) is a trait-mark behavior that successfully breeds in rodents. Here, 'congenital' LH (cLH) rats were trained to recognize and respond to 12s long interval cues (irt>12s schedule). Rats compliant to an irt>t schedule will space responses evenly and respond rhythmically. Irt>t schedule derived data are plotted in histograms showing irt (interresponse time) frequencies. A pause response peak emerges, for outbred rats, at irt values approximating the minimum interval for reinforcement. cLH rats [n=9] complied poorly to schedule contingencies when diluent (vehicle) was injected before testing. Moderate and high dose injections of a CB 1 receptor selective agonist drug (AM 411), however, increased operant schedule compliance and normalized the cLH rats' irt>t histogram distributions. Performance indicators for cLH rats are presented alongside coordinate measures from a comparison group [n=5] of normally bred Sprague-Dawley (SD) rats. In both cLH and SD rats, treatment session histograms revealed shifts of the pause response peak not accompanied by a change in motor responsiveness. The irt>12s histogram shifts were absent when AM 411 dosages were arranged to follow pre-medication injections of a CB 1 receptor selective antagonist drug (AM 251). In short, AM 411 increased timing acuity in rats prone to behavioral despair but had opposite timing effects in normally bred SD rats.
C B Willmore; G D Kohler; A Makriyannis
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-06-06
Journal Detail:
Title:  Neuropharmacology     Volume:  51     ISSN:  0028-3908     ISO Abbreviation:  Neuropharmacology     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-06-23     Completed Date:  2006-09-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0236217     Medline TA:  Neuropharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  90-101     Citation Subset:  IM    
University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD 21201, USA.
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MeSH Terms
Adamantane / analogs & derivatives*,  antagonists & inhibitors,  pharmacology
Conditioning, Operant / drug effects*
Data Interpretation, Statistical
Dose-Response Relationship, Drug
Helplessness, Learned*
Motor Activity / drug effects
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1 / agonists*,  antagonists & inhibitors*
Reinforcement Schedule
Tetrahydrocannabinol / analogs & derivatives*,  antagonists & inhibitors,  pharmacology
Grant Support
Reg. No./Substance:
0/(-)-adamantyl-delta8-tetrahydrocannabinol; 0/Receptor, Cannabinoid, CB1; 1972-08-3/Tetrahydrocannabinol; 281-23-2/Adamantane

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