A new paper from the Fantegrossi laboratory examines the behavioral and physiological effects of the substituted cathinone drug, and "bath salts" constituent, 3,4-methylenedioxypyrovalerone (MDPV) [ Search PubMed ] which is the compound which has dominated the US media reports of averse consequences of bath salts intoxication. To the extent that verification of the drug has been provided in such reports, of course. Additional confirmation can be found here, here.
The current issue of Neuropsychopharmacology has a bath salts image on the cover and contains an article from Baumann and colleagues on MDPV pharmacology (I discussed it here) and this paper from Fantegrossi and colleagues.
William E Fantegrossi, Brenda M Gannon, Sarah M Zimmerman and Kenner C Rice In vivo Effects of Abused ‘Bath Salt’ Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity. Neuropsychopharmacology (2013) 38, 563–573; doi:10.1038/npp.2012.233; published online 5 December 2012 [ ArticleLink(free); PDF ]
This is a behavioral pharmacology study in male NIH Swiss mice which first uses drug discrimination techniques to show that when mice are trained to discriminate 0.3 mg/kg i.p. MDPV from saline the subsequent dose response curves for 0.01 to 0.3 mg/kg of MDPV, METH and MDMA are nearly identical. This article has been made freely available so I won't belabor this part of the study.
What I wanted to focus on was the radiotelemetry studies of body temperature and locomotion. For reasons related to this classic paper on MDMA from Malberg and Seiden, most investigations of the effects of stimulant drugs in rodents should include some consideration of the role of ambient temperature. Fantegrossi and colleagues examined the effects of 0.3-30 mg/kg i.p. MDPV at both 20°C and 28°C. They showed, first of all, that MDPV produces no change in body temperature when administered at 20°C, but induces temperature elevations in a dose-dependent manner when animals are evaluated at 28°C. Even more interesting is what is shown in Figure 4 which I've included here. You can see that the locomotor stimulant effect (total activity counts over 6 hrs; left panel) of MDPV also is more pronounced at the higher ambient temperature with a peak differential observed after the 10 mg/kg i.p. dose (timecourse for this dose shown in right panel). There were also some other interesting phenomenological differences observed with the high ambient temperature condition.
At the highest tested dose of MDPV (30 mg/kg), significant focused stereotypy was observed at 28 1C, but not at 20 1C. Furthermore, four (of six) mice treated with 30 mg/kg MDPV at the high ambient temperature engaged in skin-picking and self-biting, which drew blood, and, in accordance with our IACUC approval, were removed from the study and euthanized. No signs of self-injurious behavior were observed at any dose of MDPV administered at 20 1C.
Repetitive, stereotyped behavior is common with locomotor stimulants and can be observed following high doses of amphetamine, methamphetamine and cocaine among other compounds. So this is probably an expected effect. What was interesting here was the dependency on ambient temperature. Off the top of my head, I can't remember either the stimulant drug sterotypy literature (which focuses on charcterizing the repetitive behaviors) or the locomotor studies (where the "inverted U" dose effect function often reflects the emergence of stereotyped behavior after high doses) focusing too heavily on the ambient temperature issue. No doubt I could stand to go back and review some papers with a closer eye on the ambient temperature.
This study, however, points a finger at environmental issues when trying to figure out the degree to which the drug MDPV might cause sensational media-friendly outcomes in some users. Studies such as the present one may indicate that factors as subtle as how hot it is the day a person takes a given drug can change the experience from relatively benign into something much more severe. Thus, a dose of a drug which has been taken before by the same user may have highly unpredictable effects just based on this one difference in the situation.
Watterson et al 2012 demonstrated intravenous self-administration in rats.
Huang et al, 2012 showed locomotor effects of MDPV on activity wheels in rats.
Fuwa et al 2007 shows dopamine responses with microdialysis and locomotor effects [in Japanese, but the Abstract is in English and the figures are easily interpreted]
Meltzer et al 2006 present monoamine pharmacology on a series of pyrovalerone compounds
Fantegrossi WE, Gannon BM, Zimmerman SM, & Rice KC (2012). In vivo Effects of Abused 'Bath Salt' Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology PMID: 23212455