Impact of fluoxetine preexposure on MDMA-induced taste avoidance in male and female rats.

Abstract

The use of both prescription and illicit drugs creates the potential for drug interactions as a function of both pharmacokinetic and pharmacodynamic processes. One such interaction is that of fluoxetine and methylenedioxymethamphetamine (MDMA) in which fluoxetine attenuates the positive-like effects of MDMA. The present work extends the analysis of their interaction by examining the impact of fluoxetine on the aversive effects of MDMA which in balance with its rewarding effects may mediate its abuse potential. Male and female Sprague–Dawley rats were given fluoxetine (10 mg/kg every 4th day for five injections) prior to taste avoidance training with MDMA (3.2 mg/kg). MDMA induced taste avoidance in males and females (faster acquisition in females). Fluoxetine preexposure attenuated this avoidance in males, but not females. For males, the attenuation was partial as MDMA-conditioned animals with fluoxetine preexposure still displayed a significant reduction in fluid intake compared to controls. Consistent with prior work assessing the interaction of fluoxetine and MDMA, fluoxetine preexposure impacted the ability of MDMA to support taste avoidance learning, specifically attenuating the aversive effect of the drug. Prior work has shown that fluoxetine attenuates MDMA’s positive effects which might lead to reduced intake of the drug; however, the concurrent reduction in the drug’s aversive effects may still shift the overall affective balance of these two affective properties toward continued use and abuse. The fact that the attenuation was only evident in males needs further study to investigate the sex-dependent effects of drug history.

Effects of Methylone Pre-Exposure on Fluoxetine-Induced Conditioned Taste Avoidance in Male and Female Sprague-Dawley Rats

“…Ethanol pre-exposure, however, attenuated avoidance in males, but not females ([ 49 ]; see also [ 67 ]). Although no studies have addressed sex differences in the effects of drug history on fluoxetine-induced avoidance, Bowman et al [ 34 ] recently reported that pre-exposure to fluoxetine attenuated avoidance induced by MDMA only in males (females displayed MDMA-induced avoidance at levels similar to animals pre-exposed to vehicle). The fact that there was no evidence of the effects of methylone history on fluoxetine-induced avoidance in females adds to the list of such assessments and supports the position that the effects of drug history are drug- and sex-dependent.…”

“…Fluoxetine pre-exposure also attenuates MDMA-induced anxiety and depression [ 33 ]. Recently, Bowman et al [ 34 ] reported that fluoxetine pre-exposure attenuated MDMA-induced conditioned taste avoidance in males but not females. Collectively, these studies suggest an overlap of MDMA and fluoxetine neurochemical activity, specifically 5-HT.…”

“…To address this issue, methylone was administered every fourth day for a total of five injections prior to taste avoidance conditioning with fluoxetine. The present assessment was performed in both male and female Sprague-Dawley rats due to the reported sex differences with fluoxetine ([ 34 , 35 , 36 ]; for other discussions of sex as a biological variable in taste avoidance conditioning as well as in drug use and abuse; see [ 37 , 38 ]).…”

Effects of Serial Polydrug Use on the Rewarding and Aversive Effects of the Novel Synthetic Cathinone Eutylone

“…Cocaine hydrochloride and MDMA hydrochloride were synthesized and generously provided by the National Institute on Drug Abuse (NIDA) Drug Supply Program and were dissolved in isotonic saline (0.9%) and injected subcutaneously (SC) at 32 and 3.2 mg/kg, respectively. These doses were based on prior work reporting that each is effective in inducing taste avoidance (for cocaine, see [73][74][75][76]; for MDMA, see [58,[77][78][79]) and that both attenuate taste avoidance following their pre-exposure (for cocaine, see [80,81]; for MDMA, see [77]). Concentration for the cocaine solution was 2 mg/mL and for MDMA was 0.5 mg/mL.…”