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Chunk #64 — 5. Procedures for evaluating pharmacological treatments targeting alcohol abuse and dependence — 5.6. Maintenance of ethanol drinking in the operant chamber

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Animal models for medications development targeting alcohol abuse using selectively bred rat lines: neurobiological and pharmacological validity.
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Similar to home-cage testing, operant procedures allow an investigator to evaluate different phases of the addictive process. Unlike home-cage testing, because an animal must be trained to lever press for ethanol access, operant procedures can not, in general, be used to assess pharmacological manipulation of the acquisition of ethanol self-administration. However, once lever press responding for ethanol has been established, compounds targeting different neurotransmitter/neuromodulator systems can be given prior to operant sessions to examine the effects on maintenance responding for alcohol. For example, the GABAB receptor agonist, baclofen (Maccioni et al., 2008b), and positive allosteric modulators of the GABAB receptor, GS39783 (Maccioni et al., 2008b), rac-BHFF (Maccioni et al., 2010b) and BHF177 (Maccioni et al., 2009a), reduce the maintenance of ethanol operant self-administration by sP rats, see also Agabio et al. (2012). In AA rats it has been shown that centrally administered SR141716A, a CB1 cannabinoid receptor antagonist, reduces the maintenance of operant responding for ethanol (Malinen and Hyytia, 2008). And, in inbred P rats, L-152,804, an NPY Y5 receptor antagonist, reduces the maintenance of operant responding for ethanol as well (Schroeder et al., 2005b).