The overall goal of these studies was to investigate the long-term behavioral consequences of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV). More specifically, these experiments were designed to determine if MDPV exhibited pro-impulsive effects and if serotonergic treatment with specific and selective 5-HT2A agonists and antagonists would attenuate MDPV-elicited increases in impulsivity.
The first experiments used a delay discounting assay in Sprague-Dawley rats to measure if either acute, or repeated, administration of drug altered baseline impulsive choice. Rats were separated into 3 groups–an MDPV, a cocaine, and a saline group – and it was found that MDPV dose-dependently increased impulsive choice following acute administration of MDPV, and that following repeated administration, the MDPV displayed persistent changes to impulsive choice even in the absence of drug. These changes were not seen either the cocaine or saline groups, indicating that MDPV may be more effective at increasing impulsive choice than cocaine.
The second study investigated a different facet of the behavioral construct of impulsivity, impulsive action. In this set of experiments, a differential reinforcement of low rates of responding (DRL) task was used, once again in animals treated with either MDPV, cocaine, or saline. Both cocaine and MDPV dose-dependently increased impulsive action when administered acutely, with MDPV appearing to be both more potent, and more effective, than compared to cocaine. Repeated administration of both compounds resulted in increases in suppression of operant behavior, as well as persistent increases in a measure of temporal efficiency, timing error responses.
The final study attempted to introduce a pharmacological intervention that we hypothesized would result in protracted reductions in MDPV-elicited impulsivity. To this end, we tested the ability of repeated administration of either the serotonin 5-HT2A agonist 2, 5-dimethoxy-4-iodoamphetamine (DOI) or the 5-HT2A antagonist M100907 to attenuate increases in impulsive action in a DRL following acute administration of MDPV. Both acute administration of DOI and M100907 had moderate effects of DRL performance, but that repeated administration of neither compound resulted in any persistent changes to MDPV-elicited impulsivity. Future experiments aimed at analyzing brains taken from animals used in these experiments will hopefully aid in understanding these negative results.
|Advisor:||Fantegrossi, William E.|
|Commitee:||Cáceda, Ricardo, McCain, Keith, Paule, Merle G., Prather, Paul L.|
|School:||University of Arkansas for Medical Sciences|
|Department:||Interdisciplinary Biomedical Sciences|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 81/2(E), Dissertation Abstracts International|
|Subjects:||Pharmacology, Behavioral psychology|
|Keywords:||Bath salts, Cathinones, Impulsivity, MDPV|
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