The effects of ondansetron, a 5-HT3 receptor antagonist, on cognition in rodents and primates

Barnes, James L.; Costall, B.; Coughlan, J.; Domeney, A.M.; Gerrard, Philip; Kelly, M.E.; Naylor, R.J.; Onaivi, E.S.; Tomkins, D.M.; Tyers, M.B.

doi:10.1016/0091-3057(90)90385-u

Cited by 187 publications

(62 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These findings provide the second instance where learning in two tasks known to depend on an intact hippocampus is improved by a compound that facilitates induction of LTP in vivo; that is, the first study was conducted with drugs that selectively enhance operation of the AMPA variant of the glutamate receptor and thereby improved both the encoding of memory and LTP (Staubli et al, 1994a,b). Moreover, as noted above, our findings are consistent with earlier reports on the beneficial action of the 5-HT, receptor antagonist ondansetron on cognition in rodents and primates (e.g., Barnes et al, 1990;Costa11 and Naylor, 1994). In addition, humans chronically treated with ondansetron have been reported to exhibit significant improvements in some tests of cognitive performance compared to placebo controls (Crook and Lakin, 1991).…”

Section: Discussionsupporting

confidence: 82%

Effects of 5-HT3 receptor antagonism on hippocampal theta rhythm, memory, and LTP induction in the freely moving rat

1995

View full text Add to dashboard Cite

Serotonergic brainstem projections to hippocampus are thought to preferentially target and increase, via 5-HT3 receptors, the excitability of a distinct subpopulation of interneurons that primarily regulate GABAB-mediated inhibition in the dendritic region of pyramidal cells. Hippocampal slice work suggests that the between-burst hyperpolarization caused by slow (GABAB) IPSPs plays a significant role in controlling the strength of LTP induced with theta burst stimulation. According to the above observations it was assumed that blockade of hippocampal 5-HT3 receptors should reduce the hyperpolarization and thereby enhance both the frequency of the naturally occurring theta rhythm and the induction of LTP; moreover, if LTP-like mechanisms provide the substrate for certain forms of memory, such treatment was expected to facilitate learning. Each of the above predictions was tested and confirmed in the present set of experiments. The effects of ondansetron, a potent and selective antagonist of the 5- HT3 receptor, were examined on (1) frequency of the hippocampal theta rhythm, (2) induction of LTP in field CA1 of freely moving rats, and (3) retention of olfactory and spatial memory in tasks known to depend on an intact hippocampus. When injected intraperitoneally into freely moving rats, the drug reliably and significantly increased the frequency of the hippocampal theta rhythm in a dose-dependent manner. Second, at concentrations that facilitate theta frequency (100 micrograms/kg and 500 micrograms/kg), an injection of the drug 30 min prior to delivering electrical stimulation bursts significantly increased the magnitude and duration of LTP compared to that obtained in the same animals after vehicle injections.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Section: Discussionsupporting

confidence: 82%

Effects of 5-HT3 receptor antagonism on hippocampal theta rhythm, memory, and LTP induction in the freely moving rat

1995

View full text Add to dashboard Cite

show abstract

“…In particular, DAU 6215 has been shown to act as an anxiolytic in animal models , and, like other 5-HT3 antagonists (Barnes et al, 1990;Chugh et al, 1991;Domeney et al, 1991;Carey et al, 1992), it exerts a cognition enhancing effect Pitsikas et al, 1993;1994). The results of our investigation showing the antagonism of the 5-HT-mediated inhibition of LTP, a phenomenon of synaptic plasticity possibly involved in learning (Teyler & DiScenna 1987), may provide a cellular correlate for the pharmacological effects of DAU 6215 on cognition.…”

Section: Discussionmentioning

confidence: 64%

Effects of DAU 6215, a novel 5‐hydroxytryptamine₃ (5‐HT₃) antagonist on electrophysiological properties of the rat hippocampus

Passani

Pugliese

Azzurrini

et al. 1994

British J Pharmacology

View full text Add to dashboard Cite

1 The aim of the present study was to test the effects of DAU 6215 (endo-N-(8-methyl-8-azabicyclo-[3.2.1]-octo-3-yl)-2,3-dihydro-2-oxo-lH-benzimidazole-1-carboxamide hydrochloride), a newly synthesized, selective aminophosphonovaleric acid (APV; 501M) and 6,7-dinitroquinoxaline-2,3-dione (DNQX; 25 tiM), and were elicited by the selective 5-HT3 agonist, 2-methyl-5-HT (2-Me-5-HT, 50 pM).5 The increase in frequency of s.p.s.ps induced by 5-HT was significantly antagonized by DAU 6215 in 70% of the cases, whereas the 5-HT3 antagonist always suppressed the effect of 2-Me-5-HT, at concentrations as low as 60 nM. 6 The antagonistic effect of DAU 6215 was also tested on the 5-HT3-mediated block of induction of long-term potentiation (LTP), elicited by a primed burst (PB) stimulation. Extracellular recordings showed that low concentrations (60 nM) of DAU 6215 suppressed the inhibitory action of 5-HT on PB-induced LTP, without affecting the 5-HTlA-induced reduction in the amplitude of the population spike. 7 These results provide evidence that DAU 6215 is an effective antagonist of the 5-HT3-mediated responses in the central nervous system and may offer a cellular correlate for the pharmacological effects of DAU 6215 as an anxiolytic and cognition enhancer.

show abstract

“…Similarly, systemic administration of the 5-HT 1A receptor agonist 8-OH-DPAT impaired serial reversal learning by enhancing perseverative tendencies, an effect which was reversed by the selective 5-HT 1A receptor antagonist WAY100635 (Clarke et al, 2003). Deficits were found in 5-HT-deficient rats following a tryptophan-deficient diet and monkeys with high doses of the 5-HT 3 antagonist ondansetron (Barnes et al, 1990;Domeney et al, 1991). However, low doses of ondansetron (Domeney et al, 1991) and lysergic acid diethylamide (LSD) improved reversal learning (King et al, 1974), although these effects were not specific to reversal learning per se.…”

Section: Introductionmentioning

confidence: 97%

Dissociable Effects of Selective 5-HT2A and 5-HT2C Receptor Antagonists on Serial Spatial Reversal Learning in Rats

Boulougouris

Glennon

Robbins

2007

Neuropsychopharmacol

199

183

View full text Add to dashboard Cite

Serotonin (5-hydroxytryptamine, or 5-HT) is strongly implicated in the ability to shift behavior in response to changing stimulus-reward contingencies. However, there is little information on the contribution of different 5-HT receptors in reversal learning. Thus, we investigated the effects of systemic administration of the 5-HT 2A antagonist M100907 (0, 0.01, 0.03, and 0.1 mg/kg, i.p.) and the 5-HT 2C antagonist SB 242084 (0, 0.1, 0.3, and 1.0 mg/kg, i.p.) on the performance of an instrumental two-lever spatial discrimination and serial spatial reversal learning task, where both levers were presented and only one was reinforced. The rat was required to respond on the reinforced lever under a fixed ratio 3 schedule of reinforcement. Following attainment of criterion, a series of within-session reversals was presented. Neither M100907 nor SB 242084 altered performance during spatial discrimination and retention of the previously reinforced contingencies. M100907 significantly impaired reversal learning by increasing both trials to criterion (only at the highest dose) and incorrect responses to criterion in Reversal 1, a pattern of behavior manifested as increased perseverative responding on the previously reinforced lever. In contrast, SB 242084 improved reversal learning by decreasing trials and incorrect responses to criterion in Reversal 1, with significantly fewer perseverative responses. These data support the view that 5-HT 2A and 5-HT 2C receptors have distinct roles in cognitive flexibility and response inhibition. The improved performance in reversal learning observed following 5-HT 2C receptor antagonism suggests these receptors may offer the potential for therapeutic advances in a number of neuropsychiatric disorders where cognitive deficits are a feature, including obsessive-compulsive disorder.

show abstract

The effects of ondansetron, a 5-HT3 receptor antagonist, on cognition in rodents and primates

Cited by 187 publications

References 34 publications

Effects of 5-HT3 receptor antagonism on hippocampal theta rhythm, memory, and LTP induction in the freely moving rat

Effects of 5-HT3 receptor antagonism on hippocampal theta rhythm, memory, and LTP induction in the freely moving rat

Effects of DAU 6215, a novel 5‐hydroxytryptamine₃ (5‐HT₃) antagonist on electrophysiological properties of the rat hippocampus

Dissociable Effects of Selective 5-HT2A and 5-HT2C Receptor Antagonists on Serial Spatial Reversal Learning in Rats

Contact Info

Product

Resources

About

The effects of ondansetron, a 5-HT3 receptor antagonist, on cognition in rodents and primates

Cited by 187 publications

References 34 publications

Effects of 5-HT3 receptor antagonism on hippocampal theta rhythm, memory, and LTP induction in the freely moving rat

Effects of 5-HT3 receptor antagonism on hippocampal theta rhythm, memory, and LTP induction in the freely moving rat

Effects of DAU 6215, a novel 5‐hydroxytryptamine3 (5‐HT3) antagonist on electrophysiological properties of the rat hippocampus

Dissociable Effects of Selective 5-HT2A and 5-HT2C Receptor Antagonists on Serial Spatial Reversal Learning in Rats

Contact Info

Product

Resources

About

Effects of DAU 6215, a novel 5‐hydroxytryptamine₃ (5‐HT₃) antagonist on electrophysiological properties of the rat hippocampus