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Methylone pre-exposure differentially impacts the aversive effects of MDPV and MDMA in male and female Sprague-Dawley rats: Implications for abuse vulnerability.

Hayley N Manke, Katharine H Nelson, Shihui Huang, Jacob M Bailey, Sara K Bowman, Robert A Jones, Sydney E Cerveny, Kenner C Rice, Anthony L Riley

Pharmacology, biochemistry, and behavior October 2022 DOI: 10.1016/j.pbb.2022.173470 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Preclinical experimental study Peer reviewed
Population Male and female Sprague-Dawley rats
Interventions Methylone MDPV MDMA
Dose 10 mg/kg methylone; 1.8 mg/kg MDPV; 1 mg/kg MDMA
Duration Methylone pre-exposure: one injection every 4th day for a total of five injections
Measures taste avoidance
Topics MDMA
Keywords Mdpv Methylone Polydrug use Pre-exposure Taste avoidance
Key findings Methylone pre-exposure attenuated taste avoidance induced by MDPV and MDMA in male rats, with a greater effect for MDPV, and attenuated MDPV-induced avoidance in females but had no effect on MDMA-induced avoidance in females. The authors suggest a history of methylone use may reduce the aversive effects of MDPV and MDMA, with implications for polydrug use.

Abstract

Polydrug use is well documented in synthetic cathinone users, although the consequences of such use are not well characterized. In pre-clinical research, a pre-exposure to a drug has been reported to attenuate the aversive effects of other drugs which has implications for their abuse potential. The goal of the present study was to investigate the impact of pre-exposure to the synthetic cathinone methylone on the aversive effects of MDPV and MDMA. Male and female Sprague-Dawley rats were exposed to 10 mg/kg of methylone every 4th day (for a total of five injections) prior to taste avoidance training with 1.8 mg/kg of MDPV or 1 mg/kg of MDMA. MDPV and MDMA induced taste avoidance in males and females (all p's < 0.05). In males, methylone pre-exposure attenuated the avoidance induced by MDPV and MDMA (all p's < 0.05) with the attenuation greater with MDPV. In females, methylone pre-exposure attenuated avoidance induced by MDPV (all p's < 0.05), but it had no effect on those induced by MDMA (all p's > 0.05). The effects of exposure to methylone on taste avoidance induced by MDPV and MDMA were drug- (MDPV > MDMA) and sex- (MDMA only in males) dependent. The attenuating effects of methylone pre-exposure on MDPV and MDMA were discussed in terms of their shared neurochemical action. These findings suggest that a history of methylone use may reduce the aversive effects of MDPV and MDMA which may have implications for polydrug use involving the synthetic cathinones.

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