title: Irt>t schedule controlled behavior in 'learned-helpless' rats: effects from a cannabinoid agonist.
abstract: 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.
authors.affiliation: University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD 21201, USA. cwillmor@rx.umaryland.edu
authors.forename: C B
authors.initials: CB
authors.lastname: Willmore
authors.forename: G D
authors.initials: GD
authors.lastname: Kohler
authors.forename: A
authors.initials: A
authors.lastname: Makriyannis
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006380:Helplessness, Learned; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000037:antagonists & inhibitors*; D012055:Reinforcement Schedule
chemical_list: C496392:(-)-adamantyl-delta8-tetrahydrocannabinol; D043884:Receptor, Cannabinoid, CB1; D013759:Dronabinol; D000218:Adamantane