Dissociation between hypothermia and neurotoxicity caused by mephedrone and methcathinone in TPH2 knockout mice.
RATIONALE
Mephedrone is a commonly abused constituent of "bath salts" and has many pharmacological effects in common with methamphetamine. Despite their structural similarity, mephedrone differs significantly from methamphetamine in its effects on core body temperature and dopamine nerve endings. The reasons for these differences remain unclear.


OBJECTIVES
Mephedrone elicits a transient hypothermia which may provide intrinsic neuroprotection against methamphetamine-like toxicity to dopamine nerve endings. Furthermore, evidence in the literature suggests that this hypothermia is mediated by serotonin. By utilizing transgenic mice devoid of brain serotonin, we determined the contribution of this neurotransmitter to changes in core body temperature as well as its possible role in protecting against neurotoxicity. The effects of methcathinone and 4-methyl-methamphetamine, two structural analogs of mephedrone and methamphetamine, were also evaluated in these mice.


RESULTS
The hypothermia induced by mephedrone and methcathinone in wild-type mice was not observed in mice lacking brain serotonin. Despite preventing drug-induced hypothermia, the lack of serotonin did not alter the neurotoxic profiles of the test drugs.


CONCLUSIONS
Serotonin is a key mediator of pharmacological hypothermia induced by mephedrone and methcathinone, but these body temperature effects do not contribute to dopamine nerve ending damage observed in mice following treatment with mephedrone, methcathinone or 4-methyl-methamphetamine. Thus, the key component of methamphetamine neurotoxicity lacking in mephedrone remains to be elucidated.
['Anneken|John H|JH|', 'Angoa-Perez|Mariana|M|', 'Sati|Girish C|GC|', 'Crich|David|D|', 'Kuhn|Donald M|DM|http://orcid.org/0000-0002-8546-9507']
D000818:Animals D005260:Female D007035:Hypothermia D013287:Illicit Drugs D008694:Methamphetamine D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D009411:Nerve Endings D020258:Neurotoxicity Syndromes D011427:Propiophenones D014365:Tryptophan Hydroxylase
Hypothermia Neurotoxicity Mephedrone Methcathinone Dopamine 4-methyl-methamphetamine