Analysis of the role of the 5-HT1B receptor in spatial and aversive learning in the rat.
The present study examined 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 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-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.
Ahlander-Lüttgen
Maria
M
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Madjid
Nather
N
Schött
Pär A
PA
Sandin
Johan
J
Ogren
Sven Ove
SO
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001522:Behavior, Animal; D001578:Benzopyrans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D004924:Escape Reaction / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012153:Retention, Psychology / Q000187:drug effects; D012601:Scopolamine / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013028:Space Perception / Q000502:physiology*; D013550:Swimming
C112429:2-(((3-(morpholinylmethyl)-2H-chromen-8-yl)oxy)methyl)morpholine; D001578:Benzopyrans; D004338:Drug Combinations; D009025:Morpholines; D018727:Muscarinic Antagonists; D010880:Piperidines; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C075631:anpirtoline; D012601:Scopolamine