Mephedrone interactions with cocaine: prior exposure to the 'bath salt' constituent enhances cocaine-induced locomotor activation in rats - PubMed (original) (raw)

Mephedrone interactions with cocaine: prior exposure to the 'bath salt' constituent enhances cocaine-induced locomotor activation in rats

Ryan A Gregg et al. Behav Pharmacol. 2013 Dec.

Abstract

Concurrent use of mephedrone (4-methylmethcathinone; MEPH) and established drugs of abuse is now commonplace, but knowledge about interactions between these drugs is sparse. The present study was designed to test the hypothesis that prior MEPH exposure enhances the locomotor-stimulant effects of cocaine and methamphetamine (METH). For cocaine experiments, rats pretreated with saline, cocaine (15 mg/kg), or MEPH (15 mg/kg) for 5 days were injected with cocaine after 10 days of drug absence. For METH experiments, rats pretreated with saline, METH (2 mg/kg), or MEPH (15 mg/kg) were injected with METH after 10 days of drug absence. Cocaine challenge produced greater locomotor activity after pretreatment with cocaine or MEPH than after pretreatment with saline. METH challenge produced greater locomotor activity after METH pretreatment than after saline pretreatment; however, locomotor activity in rats pretreated with MEPH or saline and then challenged with METH was not significantly different. The locomotor response to MEPH (15 mg/kg) was not significantly affected by pretreatment with cocaine (15 mg/kg) or METH (0.5, 2 mg/kg). The present demonstration that cocaine-induced locomotor activation is enhanced by prior MEPH exposure suggests that MEPH cross-sensitizes to cocaine and increases cocaine efficacy. Interestingly, MEPH cross-sensitization was not bidirectional and did not extend to METH, suggesting that the phenomenon is sensitive to specific psychostimulants.

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Conflict of interest statement

Conflicts of Interest: None declared

Figures

Fig. 1

Fig. 1. Effects of MEPH and cocaine exposure on locomotor activity

1A) Rats pretreated with saline (SAL), cocaine (COC) (15 mg/kg) or MEPH (15 mg/kg) were challenged with COC (15 mg/kg). 1B) Rats pretreated with saline or COC (15 mg/kg) were challenged with MEPH (15 mg/kg). Temporal data are expressed as activity counts + S.E.M. following COC (1A) or MEPH (1B) injection (arrow). Cumulative data (box) are expressed as total activity counts following COC (0–30 min) or MEPH (0–90) injection. N=8 rats/group. ***p < 0.001, **p < 0.01 or *p < 0.05 compared to SAL/COC; +p < 0.05 compared to COC/COC.

Fig. 2

Fig. 2. Effects of MEPH and METH exposure on locomotor activity

2A) Rats pretreated with saline (SAL), METH (2 mg/kg) or MEPH (15 mg/kg) were challenged with METH (2 mg/kg). 2B) Rats pretreated with saline or METH (0.5, 2 mg/kg) were challenged with MEPH (15 mg/kg). Temporal data are expressed as activity counts + S.E.M. following METH (2A) or MEPH (2B) injection (arrow). Cumulative data (box) are expressed as total activity counts following METH (0–90 min) or MEPH (0–90) injection. N=8 rats/group. ***p < 0.001, **p < 0.01 or *p < 0.05 compared to SAL/METH; +++p < 0.001 compared to METH/METH.

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