Mephedrone ('bath salt') elicits conditioned place preference and dopamine-sensitive motor activation.
Abuse of a dangerous street drug called mephedrone (4-methylmethcathinone) has become commonplace in the United States. Mephedrone is hypothesized to possess abuse liability, share pharmacological properties with psychostimulants, and display toxicity that has been linked to fatalities and non-fatal overdoses. Knowledge about the pharmacology of mephedrone has been obtained primarily from surveys of drug abusers and emergency room visits rather than experimental studies. The present study used motor activity and conditioned place preference (CPP) assays to investigate behavioral effects of mephedrone. Acute mephedrone (3, 5, 10, 30 mg/kg, ip) administration increased ambulatory activity in rats. Mephedrone (5 mg/kg, ip)-induced ambulation was inhibited by pretreatment with a dopamine D1 receptor antagonist (SCH 23390) (0.5, 1, 2 mg/kg, ip) and enhanced by pretreatment with a dopamine D2 receptor antagonist (sulpiride) (2 mg/kg, ip). Rats injected for 5 days with low dose mephedrone (0.5 mg/kg, ip) and then challenged with mephedrone (0.5 mg/kg, ip) following 10 days of abstinence displayed sensitization of ambulatory activity. In CPP experiments, mephedrone (30 mg/kg, ip) conditioning elicited a preference shift in both rats and mice. The CPP and dopamine-sensitive motor activation produced by mephedrone is suggestive of abuse liability and indicates commonalities between the neuropharmacological profiles of mephedrone and established drugs of abuse.
Department of Pharmacology, Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Renata
R
Lisek
Wei
W
Xu
Ekaterina
E
Yuvasheva
Yi-Ting
YT
Chiu
Allen B
AB
Reitz
Lee-Yuan
LY
Liu-Chen
Scott M
SM
Rawls
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D008694:Methamphetamine; D013469:Sulpiride; C548233:mephedrone; D004298:Dopamine