Nelson LE, Franks NP, Maze M (2003) Discrete lesioning of orexin (hypocretin)-containing neurons potentiates dexmedetomidine- but not pentobarbital-induced hypnosis. Neuroscience 2003 Abstracts 426.13. Society for Neuroscience, New Orleans, LA.
Summary: Introduction: Recent work suggests that anesthetics putatively modulated by the α2-adrenoceptor (e.g. dexmedetomidine (DEX)) or the GABAA receptor (e.g. pentobarbital (PTB)) elevate and depress c-Fos expression, respectively, in the orexinergic perifornical area (PeF)1. Here the hypnotic effects of DEX and PTB are assessed after selective lesion of the PeF by orexin-B conjugated to saporin (OX-SAP). Methodology: Anesthetized Fischer rats were administered stereotaxic PeF injections of saline (0.5µl/side) or OX-SAP (490ng/0.5μl/side; as described2). Loss of righting reflex (LORR) induced by DEX (150μg/kg, SC), PTB (50mg/kg, SC), and saline was tested 1 day pre- and 1, 4, 8, and 12 days post-surgery, then lesions were assessed histologically. All data are presented as means±SEMs (n=6; comparisons by unpaired t-tests and ANOVA, Newman-Keuls). Results: Bilateral PeF lesions enhanced DEX-induced hypnosis at days 8 (281.2±15.8 min; p<0.05) and 12 (322.7±15.93 min; p<0.001) as compared to naïve (234.5±9.0 min) and saline sham animals (day 8, 236.7±9.8 min; day 12, 242.8±10.80 min). In contrast, PTB-induced LORR remained unaffected at day 12 (124.8±6.8 min) relative to naïve (119.4±4.6 min) and sham (120.8±5.3 min). These results agree with previous reports that by day 12, PeF-microinjected OX-SAP induces roughly 80% cell loss2. Conclusion: The absence of a functional PeF potentiates hypnosis induced by DEX but not PTB, as perturbation of the PeF by microinjected GABAA receptor antagonist gabazine is known to 1. References: 1 Nelson et al. (2002) SfN abstract 776.14/M20; 2 Geraschenko et al. (2001) J Neurosci 21:7273-83.
Related Products: OX7-SAP (Cat. #IT-02)