Overall, these studies aimed to understand the pharmacological mechanisms underlying the behavioral and physiological effects of bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) in mice.
The first experiments verify MDPV displays psychostimulant characteristics in animals. Mice were trained to discriminate MDPV from saline and tested with doses of MDPV, 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (METH), JWH-018, and morphine. MDMA and METH elicited MDPV-like responding, while JWH-018 and morphine did not—suggesting MDPV has psychostimulant-like interoceptive effects. In separate mice, surgically-implanted radiotelemetry probes monitored thermoregulatory and locomotor responses to MDPV as a function of ambient temperature. MDPV induced hyperactivity across ambient temperatures, but MDPV-induced hyperthermic effects were only observed under warm conditions.
The second studies aimed to determine the contribution of each enantiomer of MDPV to the previously described effects on drug discrimination, activity, and temperature. Mice trained to discriminate cocaine from saline were tested with MDPV, S(+)-MDPV, and R(–)-MDPV. These data showed both enantiomers are CNS-active (eliciting cocaine-like responding); however potency differed greatly. Locomotor activity and body temperature were unaffected by R(–)-MDPV, while S(+)-MDPV produced results analogous to MDPV, suggesting S(+)-MDPV is primarily responsible for MDPV-elicited effects.
The third study attempted to determine the role of monoaminergic systems on the locomotor stimulant and hyperthermic effects of racemic MDPV. Probe-implanted mice were pretreated with monoamine reuptake inhibitors (Fluoxetine-5-HT, desipramine-NE, or bupropion-DA) or synthesis inhibitors (pCPA-5-HT or aMPT-DA/NE) and subsequently dosed with MDPV, under different ambient temperatures. Pretreatment did not alter locomotor activity counts; however, fluoxetine and desipramine pretreatment blocked MDPV-induced hyperthermia. Thus indicating MDPV-induced locomotor stimulant effects may not result from interaction with monoamine transporters, and the effects of MDPV are possibly differentially regulated depending on ambient temperature.
The final experiments examined the locomotor, reinforcing, and appetitive stimulus effects of orally self-administered MDPV in mice. The reinforcing effects were evaluated using a continuous-access two-bottle choice paradigm, while conditioned place preference (CPP) was utilized to explore the appetitive effects of oral MDPV. MDPV concentrations sufficient to produce locomotor stimulation were preferentially consumed over quinine and elicited CPP—demonstrating oral MDPV has reinforcing effects likely related to its psychostimulant-like pharmacological profile.
|Advisor:||Fantegrossi, William E.|
|Commitee:||McCain, Keith, Paule, Merle, Peterson, Eric C., Wesinger, William D.|
|School:||University of Arkansas for Medical Sciences|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 77/11(E), Dissertation Abstracts International|
|Keywords:||Bath salts, Behavior, MDPV, Monoamines, Stimulants|
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