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  4. Lesions of basal forebrain cholinergic neurons eliminate the modulatory effects of benzodiazepine receptor ligands on behavioral and cardiovascular reactions in an anxiogenic paradigm.

Lesions of basal forebrain cholinergic neurons eliminate the modulatory effects of benzodiazepine receptor ligands on behavioral and cardiovascular reactions in an anxiogenic paradigm.

Stowell JR, Bemtson GG, Sarter M (1999) Lesions of basal forebrain cholinergic neurons eliminate the modulatory effects of benzodiazepine receptor ligands on behavioral and cardiovascular reactions in an anxiogenic paradigm. Neuroscience 1999 Abstracts 358.5. Society for Neuroscience, Miami, FL.

Summary: We have previously shown that basal forebrain cortical cholinergic projections mediate potentiation of the cardiovascular defensive response by the putative anxiogenic benzodiazepine receptor partial inverse agonist FG 7142 (Bertnson et al., 1998). The present study assessed the effects of lesions of the basal forebrain cholinergic neurons on operant responding in a conditioned suppression paradigm and the modulating effects of benzodiazepine receptor (BZR) ligands in this paradigm. Nine animals received basal forebrain infusions (0.18 µg/hemisphere) of the immunotoxin 192 IgG-saporin. Lesioned and control (n=9) animals were trained in a conditioned suppression paradigm using a tone for the conditioned stimulus (CS) and a rear panel light for a contextual cue. FG 7142 (8 mg/kg), chlordiazepoxide (CDP, 8 mg/kg), and vehicle were administered i.p. in subsequent extinction sessions. In control animals, operant responding was suppressed during presentation of the CS and contextual cue. The BZR partial inverse agonist FG 7142 exaggerated this suppression,while CDP attenuated it. Lesioned animals were less suppressed than controls across stimulus conditions, with the largest difference between groups observed during presentation of the contextual cue. Presentation of the contextual cue was also associated with a cardioacceleratory response in control animals, and this response was significantly attenuated in lesioned animals. Furthermore, the modulatory effects of BZR ligands on behavioral and autonomic reactions observed in control animals were eliminated in lesioned animals. These data support an important role for cholinergic basal forebrain neurons in the behavioral and autonomic response to anxiety. Funded by HL54428.

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

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