Cholinergic stimulation of substantia nigra

abolition of carbachol-induced eating by unilateral 6-hydroxydopamine lesion of nigrostriatal dopamine neurones

G. C. Parker, E. L. Rugg, P. Winn

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16 Citations (Scopus)

Abstract

Microinjection of cholinergic agonists into the substantia nigra is known to elicit increases in eating, drinking and sexual behaviour under appropriate circumstances. It has been suggested that these effects are dependent on stimulation of nigrostriatal dopamine-containing neurones in the substantia nigra pars compacta, but no direct evidence has confirmed this. The present experiment was therefore undertaken to determine whether unilateral lesions of nigrostriatal dopamine neurones made by 6-hydroxydopamine would attenuate or abolish eating in satiated rats elicited by intranigral microinjection of the muscarinic agonist carbachol. Two groups of rats were tested: a 6-hydroxydopamine- and a sham-lesion group. Before lesions were made intranigral microinjection of 0.5 μg/0.5 μl carbachol stimulated significantly more eating than control microinjections in both groups. After 6-hydroxydopamine lesions, microinjection of carbachol elicited no more eating than vehicle alone. Rats given sham lesions (ascorbate-saline vehicle only) showed increased feeding to intra-nigral carbachol before and after sham-lesioning. Post-mortem analysis by HPLC was used to determine the concentration of dopamine, DOPAC, HVA, serotonin and 5-HIAA in the lesioned and nonlesioned hemispheres of both 6-hydroxydopamine- and sham-lesioned rats. In caudate-putamen there were significant reductions in the concentration of DA (to 50.03% of the level in control sides), DOPAC (to 49.34%) and HVA (to 63.98%) in the 6-hydroxydopamine-lesioned but not sham-lesioned rats. The concentration of dopamine, DOPAC and HVA were not affected in the nucleus accumbens. The turnover of dopamine (assessed by calculating the ratio of dopamine to DOPAC) in the caudateputamen but not nucleus accumbens was also altered by the 6-hydroxydopamine lesions. The concentration and turnover of serotonin was not affected in either the caudate-putamen or nucleus accumbens in either group of rats. These data show that loss of dopamine from the caudate-putamen but not nucleus accumbens is sufficient to abolish completely the eating stimulated by intranigral carbachol.

Original languageEnglish
Pages (from-to)597-603
Number of pages7
JournalExperimental Brain Research
Volume87
Issue number3
DOIs
Publication statusPublished - 1 Dec 1991

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Oxidopamine
Dopaminergic Neurons
Carbachol
Substantia Nigra
Cholinergic Agents
Microinjections
3,4-Dihydroxyphenylacetic Acid
Eating
Nucleus Accumbens
Dopamine
Putamen
Serotonin
Cholinergic Agonists
Muscarinic Agonists
Drinking Behavior
Hydroxyindoleacetic Acid
Feeding Behavior
Sexual Behavior
High Pressure Liquid Chromatography

Keywords

  • 6-hydroxydopamine
  • carbachol
  • dopamine
  • eating
  • HPLC
  • substantia nigra
  • 3,4 dihydroxyphenylacetic acid
  • 5 hydroxyindoleacetic acid
  • dexamphetamine
  • haloperidol
  • homovanillic acid
  • oxidopamine
  • serotonin
  • animal experiment
  • cholinergic stimulation
  • dose response
  • nerve cell stimulation

Cite this

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title = "Cholinergic stimulation of substantia nigra: abolition of carbachol-induced eating by unilateral 6-hydroxydopamine lesion of nigrostriatal dopamine neurones",
abstract = "Microinjection of cholinergic agonists into the substantia nigra is known to elicit increases in eating, drinking and sexual behaviour under appropriate circumstances. It has been suggested that these effects are dependent on stimulation of nigrostriatal dopamine-containing neurones in the substantia nigra pars compacta, but no direct evidence has confirmed this. The present experiment was therefore undertaken to determine whether unilateral lesions of nigrostriatal dopamine neurones made by 6-hydroxydopamine would attenuate or abolish eating in satiated rats elicited by intranigral microinjection of the muscarinic agonist carbachol. Two groups of rats were tested: a 6-hydroxydopamine- and a sham-lesion group. Before lesions were made intranigral microinjection of 0.5 μg/0.5 μl carbachol stimulated significantly more eating than control microinjections in both groups. After 6-hydroxydopamine lesions, microinjection of carbachol elicited no more eating than vehicle alone. Rats given sham lesions (ascorbate-saline vehicle only) showed increased feeding to intra-nigral carbachol before and after sham-lesioning. Post-mortem analysis by HPLC was used to determine the concentration of dopamine, DOPAC, HVA, serotonin and 5-HIAA in the lesioned and nonlesioned hemispheres of both 6-hydroxydopamine- and sham-lesioned rats. In caudate-putamen there were significant reductions in the concentration of DA (to 50.03{\%} of the level in control sides), DOPAC (to 49.34{\%}) and HVA (to 63.98{\%}) in the 6-hydroxydopamine-lesioned but not sham-lesioned rats. The concentration of dopamine, DOPAC and HVA were not affected in the nucleus accumbens. The turnover of dopamine (assessed by calculating the ratio of dopamine to DOPAC) in the caudateputamen but not nucleus accumbens was also altered by the 6-hydroxydopamine lesions. The concentration and turnover of serotonin was not affected in either the caudate-putamen or nucleus accumbens in either group of rats. These data show that loss of dopamine from the caudate-putamen but not nucleus accumbens is sufficient to abolish completely the eating stimulated by intranigral carbachol.",
keywords = "6-hydroxydopamine, carbachol, dopamine, eating, HPLC, substantia nigra, 3,4 dihydroxyphenylacetic acid, 5 hydroxyindoleacetic acid, dexamphetamine, haloperidol, homovanillic acid, oxidopamine, serotonin, animal experiment, cholinergic stimulation, dose response, nerve cell stimulation",
author = "Parker, {G. C.} and Rugg, {E. L.} and P. Winn",
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TY - JOUR

T1 - Cholinergic stimulation of substantia nigra

T2 - abolition of carbachol-induced eating by unilateral 6-hydroxydopamine lesion of nigrostriatal dopamine neurones

AU - Parker, G. C.

AU - Rugg, E. L.

AU - Winn, P.

PY - 1991/12/1

Y1 - 1991/12/1

N2 - Microinjection of cholinergic agonists into the substantia nigra is known to elicit increases in eating, drinking and sexual behaviour under appropriate circumstances. It has been suggested that these effects are dependent on stimulation of nigrostriatal dopamine-containing neurones in the substantia nigra pars compacta, but no direct evidence has confirmed this. The present experiment was therefore undertaken to determine whether unilateral lesions of nigrostriatal dopamine neurones made by 6-hydroxydopamine would attenuate or abolish eating in satiated rats elicited by intranigral microinjection of the muscarinic agonist carbachol. Two groups of rats were tested: a 6-hydroxydopamine- and a sham-lesion group. Before lesions were made intranigral microinjection of 0.5 μg/0.5 μl carbachol stimulated significantly more eating than control microinjections in both groups. After 6-hydroxydopamine lesions, microinjection of carbachol elicited no more eating than vehicle alone. Rats given sham lesions (ascorbate-saline vehicle only) showed increased feeding to intra-nigral carbachol before and after sham-lesioning. Post-mortem analysis by HPLC was used to determine the concentration of dopamine, DOPAC, HVA, serotonin and 5-HIAA in the lesioned and nonlesioned hemispheres of both 6-hydroxydopamine- and sham-lesioned rats. In caudate-putamen there were significant reductions in the concentration of DA (to 50.03% of the level in control sides), DOPAC (to 49.34%) and HVA (to 63.98%) in the 6-hydroxydopamine-lesioned but not sham-lesioned rats. The concentration of dopamine, DOPAC and HVA were not affected in the nucleus accumbens. The turnover of dopamine (assessed by calculating the ratio of dopamine to DOPAC) in the caudateputamen but not nucleus accumbens was also altered by the 6-hydroxydopamine lesions. The concentration and turnover of serotonin was not affected in either the caudate-putamen or nucleus accumbens in either group of rats. These data show that loss of dopamine from the caudate-putamen but not nucleus accumbens is sufficient to abolish completely the eating stimulated by intranigral carbachol.

AB - Microinjection of cholinergic agonists into the substantia nigra is known to elicit increases in eating, drinking and sexual behaviour under appropriate circumstances. It has been suggested that these effects are dependent on stimulation of nigrostriatal dopamine-containing neurones in the substantia nigra pars compacta, but no direct evidence has confirmed this. The present experiment was therefore undertaken to determine whether unilateral lesions of nigrostriatal dopamine neurones made by 6-hydroxydopamine would attenuate or abolish eating in satiated rats elicited by intranigral microinjection of the muscarinic agonist carbachol. Two groups of rats were tested: a 6-hydroxydopamine- and a sham-lesion group. Before lesions were made intranigral microinjection of 0.5 μg/0.5 μl carbachol stimulated significantly more eating than control microinjections in both groups. After 6-hydroxydopamine lesions, microinjection of carbachol elicited no more eating than vehicle alone. Rats given sham lesions (ascorbate-saline vehicle only) showed increased feeding to intra-nigral carbachol before and after sham-lesioning. Post-mortem analysis by HPLC was used to determine the concentration of dopamine, DOPAC, HVA, serotonin and 5-HIAA in the lesioned and nonlesioned hemispheres of both 6-hydroxydopamine- and sham-lesioned rats. In caudate-putamen there were significant reductions in the concentration of DA (to 50.03% of the level in control sides), DOPAC (to 49.34%) and HVA (to 63.98%) in the 6-hydroxydopamine-lesioned but not sham-lesioned rats. The concentration of dopamine, DOPAC and HVA were not affected in the nucleus accumbens. The turnover of dopamine (assessed by calculating the ratio of dopamine to DOPAC) in the caudateputamen but not nucleus accumbens was also altered by the 6-hydroxydopamine lesions. The concentration and turnover of serotonin was not affected in either the caudate-putamen or nucleus accumbens in either group of rats. These data show that loss of dopamine from the caudate-putamen but not nucleus accumbens is sufficient to abolish completely the eating stimulated by intranigral carbachol.

KW - 6-hydroxydopamine

KW - carbachol

KW - dopamine

KW - eating

KW - HPLC

KW - substantia nigra

KW - 3,4 dihydroxyphenylacetic acid

KW - 5 hydroxyindoleacetic acid

KW - dexamphetamine

KW - haloperidol

KW - homovanillic acid

KW - oxidopamine

KW - serotonin

KW - animal experiment

KW - cholinergic stimulation

KW - dose response

KW - nerve cell stimulation

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U2 - 10.1007/BF00227084

DO - 10.1007/BF00227084

M3 - Article

VL - 87

SP - 597

EP - 603

JO - Experimental Brain Research

JF - Experimental Brain Research

SN - 0014-4819

IS - 3

ER -