Effects of some cholinergic agonists on neocortical slow wave activity in rats with basal forebrain lesions

doi:10.1016/0361-9230(93)90118-U

Brain Research Bulletin

Volume 31, Issue 5, 1993, Pages 515-521

https://doi.org/10.1016/0361-9230(93)90118-U Get rights and content

Abstract

Chronic rats, prepared with unilateral injections of kainic acid in the left basal forebrain, displayed prominent large amplitude slow wave activity in the neocortex ipsilateral to the injection. Oxotremorine and pilocarpine, given systemically following pretreatment with methyl scopolamine to block peripheral muscarinic effects, restored low voltage fast activity (LVFA) in a dose-related manner. Oxotremorine was more potent than pilocarpine. Arecoline was not consistently effective. Tetrahydroaminoacridine abolished abnormal 4–6 Hz rhythmical slow waves in the left neocortex but had little effect on large amplitude irregular slow waves. Direct-acting cholinergic agonists can restore near-normal neocortical activity after extensive cholinergic deafferentation of the neocortex.

References (37)

A. Herz
Excitation and inhibition of cholinoceptive brain structures and its relationship to pharmacological induced behavior changes
Int. J. Neuropharmacol.
(1963)
A. Herz et al.
The importance of lipid-solubility for the central action of cholinolytic drugs
Int. J. Neuropharmacol.
(1965)
P. Kellaway et al.
Electrical activity of the isolated cerebral hemisphere and isolated thalamus
Exp. Neurol.
(1966)
A.I. Levey et al.
Cholinergic nucleus basalis neurons may influence the cortex via the thalamus
Neurosci. Lett.
(1987)
F. Mitchelson
Muscarinic receptor differentiation
Pharmacol. Ther.
(1988)
P. Riekkinen et al.
The cholinergic system and EEG slow waves
Electroencephalogr. Clin. Neurophysiol.
(1991)
P. Riekkinen et al.
EEG changes induced by acute and chronic quisqualic or ibotenic acid nucleus basalis lesions are stabilized by tacridine
Brain Res.
(1991)
P. Riekkinen et al.
Effects of atipamezole and tetrahydroaminoacridine on nucleus basalis lesion-induced EEG changes
Brain Res. Bull.
(1991)
K. Semba et al.
Synchrony among rhythmical facial tremor, neocortical ‘alpha’ waves, and thalamic non-sensory neuronal bursts in intact awake rats
Brain Res.
(1980)
D.J. Stewart et al.
Cholinergic activation of the electrocorticogram: Role of the substantia innominata and effects of atropine and quinuclidinyl benzilate
Brain Res.
(1984)

C.H. Vanderwolf

Cerebral activity and behavior: Control by central cholinergic and serotonergic systems

Int. Rev. Neurobiol.

(1988)

C.H. Vanderwolf et al.

Phenoxybenzamine reduces mortality associated with intracerebral injections of excitatory neurotoxins

Pharmacol. Biochem. Behav.

(1991)

C.H. Vanderwolf et al.

Thalamic control of neocortical activation: A critical re-evaluation

Brain Res. Bull.

(1988)

I.Q. Whishaw et al.

Hippocampal EEG and behavior: Effects of variation in body temperature and relation of EEG to vibrissae movement, swimming and shivering

Physiol. Behav.

(1971)

N.J. Woolf et al.

Cholinergic systems in the rat brain: III. Projections from the pontomesencephalic tegmentun to the thalamus, tectum, basal ganglia, and basal forebrain

Brain Res. Bull.

(1986)

P. Andersen et al.

Physiological basis of the alpha rhythm

(1968)

N.J.M. Birdsall et al.

The binding of agonists to brain muscarinic receptors

Mol. Pharmacol.

(1978)

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ArticleEffects of some cholinergic agonists on neocortical slow wave activity in rats with basal forebrain lesions

Abstract

Int. J. Neuropharmacol.

Int. J. Neuropharmacol.

Exp. Neurol.

Neurosci. Lett.

Pharmacol. Ther.

Electroencephalogr. Clin. Neurophysiol.

Brain Res.

Brain Res. Bull.

Brain Res.

Brain Res.

Int. Rev. Neurobiol.

Pharmacol. Biochem. Behav.

Brain Res. Bull.

Physiol. Behav.

Brain Res. Bull.

Physiological basis of the alpha rhythm

The binding of agonists to brain muscarinic receptors

Mol. Pharmacol.

Article
Effects of some cholinergic agonists on neocortical slow wave activity in rats with basal forebrain lesions