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

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.

Dendritic colocalisation of serotonin1B receptors and the glutamate NMDA receptor subunit NR1 within the hippocampal dentate gyrus: An ultrastructural study

“…The even 5-HT 1B R distribution found across the molecular layer is also suggestive of localisation to granule cell processes which innervate throughout. Further investigation is required to identify the neurotransmitters present within 5-HT 1B R positive terminals as it is possible that some of these are the cholinergic terminals identified in other studies (Ahlander-Luttgen et al, 2003;Hu et al, 2007;Maura and Raiteri, 1986;Rutz et al, 2006;Wolff et al, 2003a,b).…”

“…Despite a focus on links between serotonergic and cholinergic transmitter systems (Ahlander-Luttgen et al, 2003;Hu et al, 2007;Rutz et al, 2006;Wolff et al, 2003a,b), modulation of glutamatergic currents has also been demonstrated in a variety of brain regions (Bouryi and Lewis, 2003;Lemos et al, 2006;Li and Bayliss, 1998;Muramatsu et al, 1998). Here, it is thought that 5-HT 1B R activation exerts an effect through pre-synaptic mechanisms, predominantly via action as inhibitory auto-and/or heteroreceptors, thereby modulating neurotransmitter release (Sari, 2004).…”

A Pharmacological Analysis of an Associative Learning Task: 5-HT1to 5-HT7Receptor Subtypes Function on a Pavlovian/Instrumental Autoshaped Memory

“…Cold Spring Harbor Laboratory Press on May 12, 2018 -Published by learnmem.cshlp.org Downloaded from solidation, and retrieval may be impaired by 5-HT 1A or 5-HT 1B (Ahlander-Luttgen et al 2003) receptor stimulation, whereas blockade of 5-HT 1A or 5-HT 2A/2B/2C receptors has no effect. 5-HT 3 antagonists or 5-HT 4 agonists (systemic or central) improved PA learning and/or prevented scopolamine-or hypoxic-induced amnesia.…”

“…Operant autoshaping-task mice lacking 5-HT 1A or 5-HT 1B receptors learn faster than do wild-type mice (Pattij 2002), but 5-HT 1A KO mice showed deficits in hippocampal-dependent learning and memory tests (Sarnyai et al 2000). 5-HT 1B KO mice showed WM enhanced-platform acquisition and probe trial performance (Buhot et al 2000), and selective 5-HT 1B antagonists facilitated WM (Ahlander-Luttgen et al 2003) and autoshaped memory (Table 3). In parallel to the finding that 5-HT 2B/2C receptor antagonist (Table 3) had no effect on autoshaped memory, 5-HT 2C receptor KO mice showed normal hidden-platform and preference for the target quadrant during a probe trial.…”

Integrated Strategy for Use of Positron Emission Tomography in Nonhuman Primates to Confirm Multitarget Occupancy of Novel Psychotropic Drugs: An Example with AZD3676

“…1)] is a high-affinity antagonist at both the serotonin (5-HT) 5-HT 1A and 5-HT 1B receptors that was developed for the treatment of cognitive impairment in Alzheimer's disease. As antagonists at the 5-HT 1A and 5-HT 1B receptors have been found to enhance learning and memory through independent mechanisms in animal models (Åhlander-Lüttgen et al, 2003;Ögren et al, 2008), our project was initiated based on the hypothesis that antagonism at both these receptors may provide more efficacious pharmacologic treatment than a compound selective for any of the receptors.…”