The neurobiology of opiate reinforcement.
ABSTRACT This article provides a basic introduction into two commonly used behavioral paradigms used for the assessment of the reinforcing and rewarding effects of drugs in experimental animals. Behavioral as well as neurochemical data regarding the neural basis of opiate reward are then critically reviewed in order to evaluate the neuroanatomical and neurochemical substrates mediating the primary and conditioned reinforcing effects of opiates as well as current hypotheses of drug-induced reward and aversion.
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ABSTRACT: Enhancing the effects of endogenously-released cannabinoid ligands in the brain might provide therapeutic effects more safely and effectively than administering drugs that act directly at the cannabinoid receptor. Inhibitors of fatty acid amide hydrolase (FAAH) prevent the breakdown of endogenous ligands for cannabinoid receptors and peroxisome proliferator-activated receptors (PPAR), prolonging and enhancing the effects of these ligands when they are naturally released. This review considers recent research on the effects of FAAH inhibitors and PPAR activators in animal models of addiction and cognition (specifically learning and memory). These studies show that FAAH inhibitors can produce potentially therapeutic effects, some through cannabinoid receptors and some through PPAR. These effects include enhancing certain forms of learning, counteracting the rewarding effects of nicotine and alcohol, relieving symptoms of withdrawal from cannabis and other drugs, and protecting against relapse-like reinstatement of drug self-administration. Since FAAH inhibition might have a wide range of therapeutic actions but might also share some of the adverse effects of cannabis, it is noteworthy that at least one FAAH-inhibiting drug (URB597) has been found to have potentially beneficial effects but no indication of liability for abuse or dependence. Although these areas of research are new, the preliminary evidence indicates that they might lead to improved therapeutic interventions and a better understanding of the brain mechanisms underlying addiction and memory.Pharmacology [?] Therapeutics 01/2013; 138(1). DOI:10.1016/j.pharmthera.2013.01.003 · 7.75 Impact Factor
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ABSTRACT: Cocaine addiction has become a major concern in the UK as Britain tops the European 'league table' for cocaine abuse. Despite its devastating health and socio-economic consequences, no effective pharmacotherapy for treating cocaine addiction is available. Identifying neurochemical changes induced by repeated drug exposure is critical not only for understanding the transition from recreational drug use towards compulsive drug abuse but also for the development of novel targets for the treatment of the disease and especially for relapse prevention. This article focuses on the effects of chronic cocaine exposure and withdrawal on each of the endogenous opioid peptides and receptors in rodent models. In addition, we review the studies that utilized opioid peptide or receptor knockout mice in order to identify and/or clarify the role of different components of the opioid system in cocaine-addictive behaviours and in cocaine-induced alterations of brain neurochemistry. The review of these studies indicates a region-specific activation of the µ-opioid receptor system following chronic cocaine exposure, which may contribute towards the rewarding effect of the drug and possibly towards cocaine craving during withdrawal followed by relapse. Cocaine also causes a region-specific activation of the κ-opioid receptor/dynorphin system, which may antagonize the rewarding effect of the drug, and at the same time, contribute to the stress-inducing properties of the drug and the triggering of relapse. These conclusions have important implications for the development of effective pharmacotherapy for the treatment of cocaine addiction and the prevention of relapse.British Journal of Pharmacology 03/2012; 166(7):1993-2014. DOI:10.1111/j.1476-5381.2012.01952.x · 4.99 Impact Factor
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ABSTRACT: The objective of this experiment was to examine the rewarding effect of electrical stimulation of the external lateral parabrachial nucleus (LPBe) and of the lateral hypothalamus (LH) in concurrent Conditioned Place Preference (cCPP) and Brain Self-Stimulation Rewarding tasks. As expected, LH-stimulated animals readily learned cCPP tasks and developed self-stimulation behaviours following the rate-frequency procedure. As previously demonstrated, stimulation of the parabrachial complex generated rewarding or aversive behaviours in cCPP procedures. However, stimulation of this subnucleus induced consistent cCPP behaviours but not brain self-stimulation in rewarding LPBe animals. These results are analysed in the context of the different natural and artificial rewarding effects found in the LPBe nucleus.Behavioural brain research 09/2009; 205(2):443-9. DOI:10.1016/j.bbr.2009.07.028 · 3.39 Impact Factor