Rats avoid intake of a saccharin conditioned stimulus (CS) when paired with a drug of abuse (LeMagnen, 1969;for reviews, see Gamzu, Vincent, &Boff, 1985;Goudie, 1987;Hunt &Amit, 1987). For decades, the suppressive effects of drugs of abuse on CS intake have been attributed to presumed aversive drug properties (Lester, Nachman, &LeMagnen, 1970). Data gleaned over the past decade, however, have provided substantive support for the hypothesis that rats avoid intake of the taste cue because the tastant is devalued in anticipation of the availability of the highly rewarding properties of the abused substance (Grigson, 1997;for review, see Grigson et al., 2008;Grigson, in press). As such, the present model serves as a unique model for the systematic study of drug-induced devaluation of natural rewards. New data, however, suggest that there may be a second process contributing to devaluation of the taste cue and this process includes an element of aversion (Wheeler et al., 2008). We hypothesize, then, that there are two processes: Devaluation of the taste cue by the highly rewarding drug properties and devaluation of the taste cue as it becomes associated with craving and withdrawal in anticipation of the impending availability of drug. The goal here is to identify the underlying circuitry. Lesion data collected over the last funding period clearly demonstrate an essential role for the gustatory thalamocortical loop (Schroy et al., 2005;Geddes et al., 2008;Geddes et al., in preparation). Even so, there is some indication that the disruptive effect of lesions of this pathway may be overridden by the use of higher doses of the drugs.
Specific Aim 1 A, 1B, and 1C will test the hypothesis that disconnection of the gustatory thalamocortical loop will disrupt the suppressive effects of low and high concentrations/doses of sweets and drugs, but not those of the illness-inducing agent, LiCl. Recent microdialysis data show that dopamine in the NAc tracks morphine-induced devaluation of the saccharin cue when morphine is administered by the experimenter (Grigson &Hajnal, 2007).
Specific Aim 2 A will use central lesions and microdialysis to test the hypothesis that the NAc depends upon an intact gustatory thalamocortical loop to track devaluation induced by self-administered cocaine. The present set of studies can be completed in 2 years. The results will: (a) Verify that an intact gustatory thalamocoritical loop is essential for devaluation induced by 'self-administered'sweets and drug;(b) Demonstrate that the disruptive effect of this lesion is retained even when using higher concentrations/ doses of rewarding sweets and drugs (i.e., cocaine and heroin);and (c) Reveal that the nucleus accumbens depends upon an intact thalamocoritical loop to track cocaine's devaluation of a sweet.
The present set of studies tests the hypothesis that an intact gustatory thalamocortical loop is essential for sweet- and drug-induced suppression of intake of an otherwise palatable saccharin cue and the accompanying shift in the neurochemical (i.e., dopamine) and electrophysiological (i.e., single cell) `code' in the nucleus accumbens.
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