Abstract
Aim: The effectiveness of nutritional supplementation on drug-seeking behavior of amphetamine-addicted rats during withdrawal was investigated using a biased conditioned place preference (CPP) paradigm. Method: Twenty-four male Sprague-Dawley rats exhibiting baseline preference for the black chamber during a 20-minute pre-conditioning exploration of the CPP box completed the study. On alternate days of an 8-day schedule, twelve rats (Group AMP) were randomly selected, given either amphetamine sulfate (5 mg/ml, i.p.) and confined to the white chamber; or vehicle (1 ml saline, i.p.) and confined to the black chamber. A significant increased percentage time spent and number of entries made by Group AMP to the drug-paired, white chamber on the test day confirmed amphetamine addiction. Group AMP subsequently received increasing doses of amphetamine over 6 days. Following acute drug withdrawal, their CPP performance was compared with that of vehicle treated rats (Group SAL). Groups AMP and SAL were equally divided and randomly assigned to animals fed chow reconstituted with the nutritional supplement (AMP-S and SAL-S) over 8 weeks or standard rat chow (AMP-N and SAL-N). CPP performances for all rats were determined blindly from video recordings following this period. Results: Nutritionally supplemented, amphetamine withdrawn rats (AMP-S) exhibited significantly decreased percentage entries and time spent in the white chamber (p < 0.05), indicating preference for the black chamber and diminished drug-seeking behavior. ANOVA revealed that after 8 weeks of dietary supplementation, AMP-S rats behaved like drug-na?ve, control animals. Conclusion: Drug-seeking behavior by amphetamine-addicted animals was eliminated after treatment with a nutritionally supplemented diet.
Highlights
Substance dependence and substance abuse, previously considered to be separate entities, have recently been incorporated into the disorder classified in the DSM-5 as Drug Addiction [1] [2]
Animals displaying at least 80% preference for the black conditioned place preference (CPP) chamber during pre-conditioning, assessed as greater number of entries and time spent in the black chamber, were selected and randomly assigned to one of two treatment groups, AMP or SAL, each containing twelve (12) rats [9] [10]
After 8 weeks of consuming the nutritional supplement, there was a significant decrease in percent entries into the drug-paired, white chamber (p < 0.05) by amphetamine withdrawn rats (AMP-S) rats, compared to SAL-S and SAL-N
Summary
Substance dependence and substance abuse, previously considered to be separate entities, have recently been incorporated into the disorder classified in the DSM-5 as Drug Addiction [1] [2]. The ability of a drug of abuse to induce reward or intoxication is initially, not solely, related to its ability to increase levels of dopamine (DA), in the nucleus accumbens of the basal forebrain This site-specific increase in DA enables the individual to predict reward, imprint incentive value to reinforcers and rapidly learn reward associations [3]. This means that the power to create an addiction does not merely lie in induction of timely hedonic pleasure, but in the evolution of complex neuroadaptations, involving DA and other neurotransmitters and receptors such as glutamate, GABA, endocannabinoids, and opioids. Research on addiction trajectories has shown that the continued use of an abused substance gradually impairs neuronal function, eventually impacting the very capacity of the drug dependent person or addict to exert free will [2]
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