Comparison of the behavioral and cardiovascular effects of mephedrone with other drugs of abuse in rats.

Abstract

RATIONALE:

Exceedingly little experimental research exists on the popular recreational drug mephedrone (4-methylmethcathinone) despite clinical reports concerning its behavioral and cardiovascular toxicity.

OBJECTIVES:

To characterize mephedrone preclinically by examining its capacity to (1) serve as a discriminative stimulus, (2) disrupt the acquisition of response sequences, and (3) disrupt mean arterial pressure (MAP) and heart rate (HR).

METHODS AND RESULTS:

In one group of subjects that reliably discriminated 3.2 mg/kg of mephedrone from saline (n = 9), substitution tests indicated that stimulants (cocaine, MDMA, and methamphetamine) more closely approximated the mephedrone discriminative stimulus than non-stimulants (fenfluramine, morphine, and phencyclidine), although none fully substituted. In a second group (n = 6), mephedrone (0.56-10 mg/kg, i.p.) dose-dependently decreased response rate and increased errors in both components of a procedure in which subjects either acquired a new response sequence each session (repeated acquisition) or completed the same response sequence each session (performance). Finally, in a third group (n = 12), radio telemetry probes were used to measure the changes in MAP and HR elicited by mephedrone and then compared them to a known stimulant, methamphetamine. In these studies, mephedrone (0.01-9 mg/kg, i.v.) elicited increases in MAP and HR that were very similar to those elicited by methamphetamine (0.01-9 mg/kg, i.v.). The tachycardia and pressor responses to mephedrone (3 mg/kg) were blocked by the β-blocker atenolol (1 mg/kg, i.v.) and the α1, α2-blocker phentolamine (3 mg/kg, i.v.), respectively.

CONCLUSIONS:

Mephedrone produces behavioral and cardiovascular responses that are similar to other stimulants; however, differences from the classical stimulants were also apparent.

• Authors: Kurt J Varner, Kyle Daigle, Peter F Weed, Peter B Lewis, Sarah E Mahne, Ananthakrishnan Sankaranarayanan, Peter J Winsauer
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 225 Issue 3 Pg. 675-85 (Feb 2013) ISSN: 1432-2072 [Electronic] Germany
• PMID: 22972412 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Illicit Drugs
• Methamphetamine
• mephedrone

Topics

• Analysis of Variance
• Animals
• Behavior, Animal (drug effects)
• Blood Pressure (drug effects)
• Conditioning, Operant (drug effects)
• Discrimination Learning (drug effects)
• Dose-Response Relationship, Drug
• Heart Rate (drug effects)
• Illicit Drugs (toxicity)
• Male
• Methamphetamine (analogs & derivatives, toxicity)
• Rats
• Rats, Long-Evans
• Rats, Sprague-Dawley