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The effects of IgG-192-saporin lesions of limbic forebrain on rat cocaine self-administration

Co C, Yin X, Johnson WE, Martin TJ, Smith JE (2003) The effects of IgG-192-saporin lesions of limbic forebrain on rat cocaine self-administration. Neuroscience 2003 Abstracts 422.3. Society for Neuroscience, New Orleans, LA.

Summary: The involvement of cholinergic neurons in cocaine self-administration has been recently demonstrated. This study was undertaken to further assess the role of cholinergic innervations of/ or interneurons in limbic brain regions previously shown to receive enhanced dopamine input during cocaine self-administration. Rats were trained to self-administer cocaine on an FR2 schedule using a within session dose intake procedure (3½ hour session with 1 hour access each to 0.17, 0.33 and 0.67 mg/infusion). The doses were then decreased systematically to threshold levels where only the highest dose was self-administered during the session. The cholinergic neurotoxin IgG-192-saporin (0.25 µg in 1 µl) or vehicle was then bilaterally administered into the posterior nucleus accumbens (NAcc) – ventral pallidum (VP). The saporin lesion resulted in a shift to the left in the dose intake relationship for cocaine self-administration with all three doses maintaining responding. The sham-vehicle treated rats continued to only sample the higher dose. Real time RT-PCR was used to assess the magnitude and extent of the lesion. Gene expression for p75 (the target for 192 IgG) and choline acetyltransferase (ChAT) were assessed in the NAcc, VP, caudate nucleus (CP) and diagonal band (DB) of these rats. Significant reductions in p75 and ChAT gene expression were seen in the DB and VP while only small decreases were seen in the NAcc and CP of the saporin treated rats. These data suggest that the overall influence of cholinergic neurons in the DB and VP are inhibitory to the processes underlying cocaine self-administration.

Related Products: 192-IgG-SAP (Cat. #IT-01)

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