Abstract
Under paradigms of combined intravenous cocaine and ethanol self-administration, the effects on behavior have been poorly explored. Numerous studies have found sex differences in amino acids profile and behavioral responses to each drug, yet few have focused on the interactions between cocaine and ethanol. The main objective of this work was to explore the acquisition and maintenance of intravenous self-administration behavior with a combination of cocaine and ethanol in male and female young adult rats. Likewise, the amino acids profile in blood plasma was quantified 48 hours after the last self-administration session. Male and female 52 days old Wistar rats were randomly assigned to one of 3 groups: i) saline control, ii) cocaine (1 mg/kg bodyweight/injection) and iii) cocaine and ethanol (1 mg + 133 mg/kg bodyweight/ injection). After 24 self-administration sessions carried out on a fixed-ratio-1 schedule, with a limit of 15 doses per session, 14 plasma amino acids were quantified by mean Capillary Electrophoresis technique. The curve of cocaine and ethanol combined self-administration was similar to that associated with cocaine administration alone, with females acquiring self-administration criterion before males. The self-administration of cocaine and ethanol altered the plasma concentration and relative ratios of the amino acid L-Tyrosine. In our intravenous self-administration model, females appeared more vulnerable to acquire abusive consumption of the cocaine and ethanol combination, which altered plasma L-Tyrosine levels.
Highlights
Despite the constant appearance of new “drugs of abuse” or “recreational drugs”, and changes in their patterns of consumption, concurrent use of cocaine and ethanol continues to be very prevalent in many countries [1], the latter representing one of the oldest recreational drugs
The percentage of female and male rats in the cocaine and ethanol (C+E) and Coc groups that met the established acquisition was assessed in each session (Fig 2)
Considering the sex factor stratified by treatment group (Coc and C+E), there were significant differences between males and females that self-administered C+E [χ2 (1, N = 40) = 4.94, p < 0.05]
Summary
Despite the constant appearance of new “drugs of abuse” or “recreational drugs”, and changes in their patterns of consumption, concurrent use of cocaine (an ester of benzoic acid and methylecgonine) and ethanol (an ethyl alcohol) continues to be very prevalent in many countries [1], the latter representing one of the oldest recreational drugs. The high prevalence of alcoholism or excessive ethanol consumption among cocaine users may be due to an attempt to mitigate some acute negative clinical symptoms of cocaine, such as anxiety, and/or to enhance other positive -and even desired- effects, such as euphoria or an improved perception of physical well-being [2, 3]. Like other forms of poly-consumption, the combined use of cocaine and ethanol (C+E) frequently begins during the transition period to adulthood and it is associated with important health consequences, in terms of the consumption or abuse of more dangerous recreational drugs. In monkeys, combined intravenous self-administration of C+E produced rates with intermediate values between cocaine and ethanol alone [5]
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