¹Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

Correspondence: Dr SO Ögren, Division of Behavioural Neuroscience, Department of Neuroscience A2:3, Karolinska Institutet, Retzius väg 8, S-171 77 Stockholm, Sweden. Tel: +46 8 7287074; Fax: +46 8 302875; E-mail: Sven.Ove.Ogren@neuro.ki.se

Received 8 January 2003; Revised 9 May 2003; Accepted 13 May 2003; Published online 2 July 2003.

Abstract

The present study examined the role of the 5-HT_1B receptor in learning and memory. The ability of the 5-HT_1B receptor agonist anpirtoline and the selective 5-HT_1B receptor antagonist NAS-181 to affect spatial learning in the water maze (WM) and aversive learning in the passive avoidance (PA) task were examined 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, 0.3 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 addition, 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-HT_1B receptor stimulation and blockade result in opposite effects in two types of cognitive tasks in the rat, and that (2) the 5-HT_1B antagonist NAS-181 can facilitate some aspects of cognitive function, most likely via an increase of cholinergic transmission. These results suggest that 5-HT_1B receptor antagonists may have a potential in the treatment of cognitive deficits resulting from loss of cholinergic transmission.