Nicotinic receptor agonists facilitate retention of avoidance training: Participation of dopaminergic mechanisms

doi:10.1016/0163-1047(93)91159-K

Behavioral and Neural Biology

Volume 59, Issue 1, January 1993, Pages 57-62

https://doi.org/10.1016/0163-1047(93)91159-K Get rights and content

The effect of nicotinic receptor agonists on retention of the inhibitory avoidance (IA) response were investigated in mice. Animals received intraperitoneal drug injections before training, and retention was evaluated 24 h later. Nicotine and cytisine, but not lobeline, significantly increased retention of the IA training. Cotinine, the main metabolite of nicotine, was inactive in the same test. Retention was not affected by the injection of the D1–D2 receptor antagonist cis-flupentixol, but the preadministration of cis-flupentixol significantly blocked the facilitatory effect of nicotine and cytisine on memory. These results demonstrate that the nicotinic receptor agonists nicotine and cytisine facilitate the retention of avoidance responses and suggest that this effect is mediated through central dopaminergic pathways.

References (39)

AboodL.G. et al.
Sites and mechanisms for nicotine's action in the brain
Neuroscience and Biobehavioral Reviews
(1981)
BuccafuscoJ. et al.
Beneficial effects of nicotine administered prior to a delayed matching-to-sample task in young and aged monkeys
Neurobiology of Aging
(1991)
CastellanoC. et al.
Post-training dopamine receptor agonists and antagonists affect memory storage in mice irrespective of their selectivity for D1 or D2 receptors
Behavioral and Neural Biology
(1991)
DaviesP. et al.
Selective loss of central cholinergic neurons in Alzheimer's disease
Lancet
(1976)
DeckerM.W. et al.
Effects of nicotine on spatial memory deficits in rats with spatial lesions
Brain Research
(1992)
DenerisE.S. et al.
Pharmacological and functional diversity of neuronal nicotinic acetylcholine receptors
Trends in Pharmacological Sciences
(1991)
FuxeK. et al.
On the action of nicotine and cotinine on central 5-hydroxytryptamine neurons
Pharmacology Biochemistry and Behavior
(1979)
LevinE.D. et al.
Cholinergic—dopaminergic interactions in cognitive performance
Behavioral and Neural Biology
(1990)
McGaughJ.L. et al.
Involvement of the amygdaloid complex in meuromodulatory influences on memory storage
Neuroscience and Biobehavioral Reviews
(1990)
McGurkS. et al.
Nicotinic-dopaminergic relationships and radial-maze performance in rats
Behavioral and Neural Biology
(1989)

ReavillC. et al.

Behavioural and pharmacokinetic studies on nicotine, cytisine and lobeline

Neuropharmacology

(1990)

RobertsonH.A.

Dopamine receptor interactions: Some implications for the treatment of Parkinson's disease

Trends in Neurosciences

(1992)

SelkoeD.J.

The molecular pathology of Alzheimer's disease

Neuron

(1991)

WhiteN.M. et al.

Localized intracaudate dopamine D2 receptor activation during the post-training period improves memory for visual or olfactory conditioned emotional responses in rats

Behavioral and Neural Biology

(1991)

WhitehouseP.J. et al.

Nicotinic acetylcholine binding sites in Alzheimer's disease

Brain Research

(1986)

AlzheimerA.

Allg. Z. Psychiatr. Psych. Gerichtl. Med.

(1907)

AndersonD.J. et al.

Neuronal nicotinic receptor binding in rat brain: A comparison of three radioligands

Society for Neuroscience Abstracts

(1991)

AndersonP.H.

Comparison of the pharmacological characteristics of [³H]raclopride and [³H]SCH23390 binding to dopamine receptors in vivo in mouse brain

European Journal of Pharmacology

(1988)

BartusR.T. et al.

The cholinergic hypothesis of geriatric memory dysfunction

Science

(1982)

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¹: We thank Dr. Michael Decker for his suggestions on earlier versions of the present manuscript and Dr. Donald Britton for his advice regarding dopaminergic agents.

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Regular articleNicotinic receptor agonists facilitate retention of avoidance training: Participation of dopaminergic mechanisms

Neuroscience and Biobehavioral Reviews

Neurobiology of Aging

Behavioral and Neural Biology

Lancet

Brain Research

Trends in Pharmacological Sciences

Pharmacology Biochemistry and Behavior

Behavioral and Neural Biology

Neuroscience and Biobehavioral Reviews

Behavioral and Neural Biology

Neuropharmacology

Trends in Neurosciences

Neuron

Behavioral and Neural Biology

Brain Research

Allg. Z. Psychiatr. Psych. Gerichtl. Med.

Neuronal nicotinic receptor binding in rat brain: A comparison of three radioligands

Society for Neuroscience Abstracts

Comparison of the pharmacological characteristics of [3H]raclopride and [3H]SCH23390 binding to dopamine receptors in vivo in mouse brain

European Journal of Pharmacology

The cholinergic hypothesis of geriatric memory dysfunction

Science

Regular article
Nicotinic receptor agonists facilitate retention of avoidance training: Participation of dopaminergic mechanisms

Comparison of the pharmacological characteristics of [³H]raclopride and [³H]SCH23390 binding to dopamine receptors in vivo in mouse brain