Neuropharmacology
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Vulnerability to the addictive effects of drugs of abuse varies among individuals, but the biological basis of these differences are poorly known. This work tries to increase this knowledge by comparing the brain proteome of animals with different rate of extinction of cocaine-seeking behaviour. To achieve this goal, we used a place-preference paradigm to separate Sprague Dawley rats in two groups: rats that extinguished (E) and rats that did not extinguish (NE) cocaine-seeking behaviour after a five-day period of drug abstinence. ⋯ When comparing E SAL and NE SAL animals we found significant differences in the expression level of 5 proteins: ATP synthase subunit alpha, fumarate hydratase, transketolase, NADH dehydrogenase [ubiquinone] flavoprotein 2 and glutathione transferase omega-1. A single injection of COC differently alters the NAC proteome of E and NE rats; thus in E COC animals there was an alteration in the expression of 6 proteins, including dihydropyrimidinase-related protein 2 and NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10; whereas in NE COC rats 9 proteins were altered (including alpha-synuclein, peroxiredoxin-2 and peroxiredoxin-5). These proteins could be potential biomarkers of individual vulnerability to cocaine abuse and may be helpful in designing new treatments for cocaine addiction.
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There is poor experimental evidence concerning the effects of anesthetic doses of the non-competitive NMDA receptor antagonist ketamine on rodents' memory abilities. The present study was designed to investigate a) the long-term consequences of anesthetic ketamine on rats' non-spatial and spatial recognition memory; b) to evaluate whether or not these effects are related to the hypothermic properties of ketamine and c) to detect when the (amnestic) effects of ketamine on recognition memory were extinguished. ⋯ Pre-training administration of ketamine (100 mg/kg; i.p.) disrupted animals' performance in the object location task and to some extent also in the object recognition paradigm indicating that anesthetic ketamine impaired both spatial and non-spatial recognition memory. Hypothermia-induced by this NMDA receptor antagonist and the type (spatial vs. non-spatial) of the behavioral paradigm utilized seem to affect rats' recognition memory recovery.