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Analysis of the Role of the 5-HT1B Receptor in Spatial and Aversive Learning in the Rat

Analysis of the Role of the 5-HT1B Receptor in Spatial and Aversive Learning in the Rat. Ahlander-Luettgen, Maria; Madjid, Nather; Schoett, Paer A.; Sandin, Johan; Oegren, Sven Ove (Department of Neuroscience, Karolinska Institutet, Stockholm, Swed.). Neuropsychopharmacology, 28(9), 1642-1655 (English) 2003 Nature Publishing Group. CODEN: NEROEW. ISSN: 0893-133X. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 2 The present study examd. the role of the 5-HT1B receptor in learning and memory. The ability of the 5-HT1B receptor agonist anpirtoline and the selective 5-HT1B receptor antagonist NAS-181 to affect spatial learning in the water maze (WM) and aversive learning in the passive avoidance (PA) task were examd. in the rat. Anpirtoline (0.1-1.0 mg/kg, s.c.) caused a dose-dependent impairment of learning and memory in both the WM and PA tasks. NAS-181 (1.0-10 mg/kg, s.c.) failed to alter performance of the WM task, but produced a dose-dependent (0.1-20 mg/kg) facilitation of PA retention. Furthermore, treatment with NAS-181 (10 mg/kg) fully blocked the impairment of the WM and PA performance caused by anpirtoline (1.0 mg/kg). In contrast, NAS-181 (3.0-10 mg/kg) did not attenuate the spatial learning deficit and the impairment of PA retention caused by scopolamine (0.1 mg/kg in WM task, 0. 205242-62-2 and 51-84-3 which are cas registry numbers of chemicals are mentioned.3 mg/kg in PA task, s.c.), a nonselective muscarinic antagonist. Moreover, a subthreshold dose of scopolamine (0.1 mg/kg) blocked the facilitation of PA retention induced by NAS-181 (1.0-10 mg/kg). In addn., the behavioral disturbances (eg thigmotaxic swimming and platform deflections) induced by anpirtoline and scopolamine were analyzed in the WM task and correlated with WM performance. These results indicate that: (1) 5-HT1B receptor stimulation and blockade result in opposite effects in two types of cognitive tasks in the rat, and that (2) the 5-HT1B antagonist NAS-181 can facilitate some aspects of cognitive function, most likely via an increase of cholinergic transmission. These results suggest that 5-HT1B receptor antagonists may have a potential in the treatment of cognitive deficits resulting from loss of cholinergic transmission. .