Hippocampal α7 and α4β2 nicotinic receptors and working memory
Section snippets
Subjects
Young adult female Sprague–Dawley rats (Taconic Farms, Germantown, NY, USA) weighing between 200 and 325 g were used in this study (study 1, n=11; study 2, n=8). The rats were housed in groups of three to four during initial training and singly after cannulation. The rat colony room had a reverse 12:12 light:dark cycle. All testing was conducted in the dark phase. The rats had ad libitum access to drinking water but were kept on a restricted feeding schedule to maintain body weights of
Study 1
Both DHβE and MLA caused a significant increase in working memory errors (Fig. 2). With MLA, a significant increase in working memory errors was seen with the high dose of 27 μg/side (F(1,30)=9.13, P<0.01). The low MLA dose (6.75 μg/side) did not cause a significant working memory impairment and the intermediate MLA (13.5 μg/side) did not cause a significant increase in working memory errors (F(1,30)=3.35, P<0.08). There was a significant linear dose–effect of MLA (P<0.05). The DHβE dose used
Discussion
These results show that significant working memory deficits can be produced by either α7 or α4β2 nicotinic receptor antagonist treatment in the ventral hippocampus. This replicates our earlier finding in the 8-arm radial maze (Felix and Levin, 1997). In that study, however, significant deficits caused by MLA and DHβE were not seen unless high doses were given. In the current study with the more challenging 16-arm maze, significant impairments were seen at lower doses of both MLA and DHβE. This
Acknowledgements
This research was supported by National Institute on Drug Abuse Grant number DA 11943.
References (42)
- et al.
Nicotine increases intracellular calcium in rat hippocampal neurons via voltage-gated calcium channels
Neurosci. Lett.
(1995) - et al.
Human α7 nicotinic acetylcholine receptor responses to novel ligands
Neuropharmacology
(1995) - et al.
Brief-lifetime fast-inactivating ion channels account for the α-bungarotoxin-sensitive nicotinic response in hippocampal neurons
Neurosci. Lett.
(1993) - et al.
Nicotinic antagonist administration into the ventral hippocampus and spatial working memory in rats
Neuroscience
(1997) - et al.
Conversion of the sodium channel activator aconitine into a potent α-7-selective nicotinic ligand
Fed. Eur. Biochem. Soc. Lett.
(1995) - et al.
A novel nicotinic agonist facilitates induction of long-term potentiation in the rat hippocampus
Neurosci. Lett.
(1994) - et al.
Nicotinic muscarinic and dopaminergic actions in the ventral hippocampus and the nucleus accumbens: Effects on spatial working memory in rats
Brain Res.
(1996) - et al.
Nicotine-dizocilpine interactions and working and reference memory performance of rats in the radial-arm maze
Pharmacol. Biochem. Behav.
(1998) - et al.
Ventral hippocampal ibotenic acid lesions block chronic nicotine-induced spatial working memory improvement in rats
Cogn. Brain Res.
(1999) - et al.
Nicotine-haloperidol interactions and cognitive performance in schizophrenics
Neuropsychopharmacology
(1996)
Cholinergic gating of response to auditory stimuli in rat hippocampus
Brain Res.
Methyllycaconitine: a selective probe for neuronal α-bungarotoxin binding sites
Fed. Eur. Biochem. Soc. Lett.
Nicotine patches in Alzheimer’s disease: pilot study on learning, memory, and safety
Pharmacol. Biochem. Behav.
The principal toxin of Delphinium brownii Rydb and its mode of action
Experientia
Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons. I. Pharmacological and functional evidence for distinct structural subtypes
J. Pharmacol. Exp. Ther.
Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons. III. Agonist actions of the novel alkaloid epibatidine and analysis of type II current
J. Pharmacol. Exp. Ther.
Choline and selective antagonists identify two subtypes of nicotinic acetylcholine receptors that modulate GABA release from CA1 interneurons in rat hippocampal slices
J. Neurosci.
Blockade of nicotinic currents in hippocampal neurons defines methyllycaconitine as a potent and specific receptor antagonist
Mol. Pharmacol.
Potential treatment of Alzheimer disease using cholinergic channel activators (ChCAs) with cognitive enhancement anxiolytic-like and cytoprotective properties
Alzheimer Dis. Assoc. Disord.
The pharmacology of (–)-nicotine and novel cholinergic channel modulators
Adv. Pharmacol.
Cognitive effects of neonatal hippocampal lesions in a rat model of schizophrenia
Neuropsychopharmacology
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