Abstract
Aim: The effect of patented nutritional supplementation on drug-seeking behavior in cocaine addicted rats during acute drug withdrawal was investigated using a biased Conditioned Place Preference (CPP) paradigm. Method: Twenty-four (24) male Sprague-Dawley rats with pre-conditioned preference for the black chamber of the CPP box were randomly divided into Cocaine (COC) or Saline (SAL) treated groups. Rats (n = 12) treated with cocaine hydrochloride 20 mg/kg/ml, i.p. (COC group) were confined individually to the white chamber on days 1, 3, 5 and 7. On alternate days, they were given 1 ml saline vehicle, i.p. and confined to the black chamber. Control rats (SAL group, n = 12) received only vehicle on all 8 days and were confined on alternate days to the white or black chamber. Positive place preference was confirmed for COC rats, which subsequently received 6 increasing daily doses of cocaine. CPP performances of both COC and SAL rats were recorded following an acute 3-day withdrawal period. All animals were then randomly assigned to rats fed either chow reconstituted with the nutritional supplement (COC-S and SAL-S) or standard rat chow (COC-N and SAL-N) for 8 weeks, followed by final CPP performances. Results: Following supplementation, COC-S rats made significantly less entries and time spent in the white chamber (p Conclusion: Drug-seeking behavior that persisted during cocaine withdrawal was significantly diminished in the nutritionally supplemented.
Highlights
Thirty-one million persons internationally suffer from substance use disorders (SUDs) with cocaine related SUDs being prevalent in the Caribbean, Latin America, North America and Western and Central Europe [1] [2]
Following 8 weeks of nutritional supplementation, cocaine-withdrawn rats (COC-S) rats spent significantly less time in (p = 0.020) and made significantly fewer entries (p = 0.001) into the drug-paired, white chamber than they did during the acute drug withdrawal period (Figure 2 and Figure 3)
Group Cocaine-withdrawn rats (COC-N) made significantly more entries into the white chamber compared with COC-S rats (p < 0.001), as well as supplemented and non-supplemented drug-naïve rats, Saline Treated Counterparts (SAL-N) and SAL-S (p < 0.001)
Summary
Thirty-one million persons internationally suffer from substance use disorders (SUDs) with cocaine related SUDs being prevalent in the Caribbean, Latin America, North America and Western and Central Europe [1] [2]. Increased activity of glutamatergic pyramidal neurons in the medial Prefrontal Cortex (mPFC) that project to the Nucleus Accumbens (NAc) has been associated with cocaine-seeking behavior in rodent models of addiction [4]. These neurons increase in synaptic plasticity following drug consumption [5]. The Conditioned Place Preference (CPP) paradigm is a well-established animal model utilized to study the role of context associations in reward-related behaviors, including both natural rewards and drugs of abuse [7] This paradigm facilitates the creation of long-term reward related memory of the drug experience in its specific context and associated stimulus [8]. The expression of cocaine-associated memory using the CPP paradigm has been linked to the activation of GABAergic neurons in the NAc [6]
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