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Biology Articles » Neurobiology » Neurobiology of Diseases & Aging » Behavioral Neurobiology of Alcohol Addiction: Recent Advances and Challenges » Novel targets

Novel targets
- Behavioral Neurobiology of Alcohol Addiction: Recent Advances and Challenges

Novel targets

Endocannabinoids

Recent evidence has shown that endogenous cannabinoids regulate ingestive behaviors via interactions with leptin (Di Marzo et al., 2001) as well as act as modulators of reward functions (De Vries et al., 2001). A number of reports now have begun to explore the specific relationship between ethanol and cannabinoid systems. Administration of the cannabinoid receptor antagonist, SR141716A, can decrease voluntary ethanol intake in mice (Arnone et al., 1997) as well as in alcohol-preferring rats (Colombo et al., 1998), where it can also prevent the acquisition of drinking behavior (Serra et al., 2001). CB1 receptors have also been shown to be involved in mediating appetitive and consummatory aspects of ethanol ingestion (Freedland et al., 2001), suggesting that SR141716A may have clinical utility in the treatment of alcohol abuse (Freedland et al., 2001). It may also be effective in the prevention of relapse, because SR141716A can be effective in inhibiting reinstatement of drug-seeking behavior elicited by cocaine or cocaine-related cues (De Vries et al., 2001). The mechanism responsible for the suppression of intake of ethanol and cocaine remains to be elucidated, although an interaction of cannabinoids with striatal DA (Giuffrida et al., 1999) is certainly a possibility, but the role of cannabinoids in leptin regulation should also be considered.

Neuropeptide Y

Neuropeptide Y (NPY), like endocannabinoids, is widely distributed throughout the brain (Dumont et al., 1992) and is involved in the control of food intake (Kalra et al., 1991). Of late, NPY has also been implicated in the regulation of ethanol consumption. NPY KO mice show increased voluntary consumption of ethanol, whereas overexpression of NPY yields the opposite result (Thiele et al., 1998). NPY KO mice were also less sensitive to ethanol-induced sedation, whereas mice overexpressing NPY had increased sleep times (Thiele et al., 1998). These effects are the result of interactions specifically with the Y1 NPY receptor subtype (Thiele et al., 2002). Consistent with these findings, rats bred for alcohol preference have reduced levels of NPY specifically within the CeA (Hwang et al., 1990), and the central infusion of exogenous NPY also decreases ethanol drinking in ethanol preferring rats (Badia-Elder et al., 2001). However, alterations of ethanol-related behaviors have not been shown when NPY was administered to nonpreferring or outbred rat strains (Slawecki et al., 2000; Badia-Elder et al., 2001), and the direct injection of NPY into the paraventricular nucleus of the hypothalamus actually increased ethanol consumption (Kelley et al., 2001). Site specificity may underlie these discrepancies, or it may be the case that NPY selectively alters the high ethanol intake of preferring rats via modulation of stress responses. Regardless of their exact mechanisms of action, both endocannabinoids and NPY are potential targets for the development of novel therapeutics for the treatment of alcohol abuse.

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