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Inhibition of the Electrically Evoked Release of [ 3 H]Acetylcholine in Rat Striatal Slices: An Experimental Model for Drugs that Enhance Dopaminergic Neurotransmission
Author(s) -
Baud P.,
Arbilla S.,
Langer S. Z.
Publication year - 1985
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1985.tb05421.x
Subject(s) - dopamine , nomifensine , acetylcholine , amphetamine , sulpiride , dopaminergic , dopamine receptor , chemistry , stimulation , autoreceptor , neurotransmitter , neurotransmission , endocrinology , dopamine receptor d2 , medicine , receptor , biology , serotonin , biochemistry
The activation by endogenous dopamine of the inhibitory 3,4‐dihydroxyphenylethylamine (dopamine) receptors modulating the electrically evoked release of [ 3 H]acetylcholine ([ 3 H]ACh) and [ 3 H]dopamine in rat striatal slices is a function of the concentration of dopamine accumulated in the synaptic cleft during electrical stimulation. When the release of 3 H‐neurotransmitters was elicited with a 2‐min period of stimulation at a frequency of 1 Hz, neither dopamine autoreceptors nor dopamine receptors modulating [ 3 H]ACh were activated by endogenously released dopamine. On the other hand, exposure to ( S )‐sulpiride facilitated the release of [ 3 H]dopamine and [ 3 H]ACh elicited when the 2‐min stimulation was carried out at a frequency of 3 Hz but this effect was not observed at a lower frequency of stimulation (1 Hz). In the presence of amphetamine the dopamine receptors modulating the electrically evoked release of [ 3 H]ACh can be activated by endogenous dopamine even at the lower frequency of stimulation (1 Hz). Similar effects can be obtained if the neuronal uptake of dopamine is inhibited by cocaine or nomifensine. The inhibition by amphetamine of the release of [ 3 H]ACh elicited by electrical stimulation at 1 Hz involves dopamine receptors and can be fully antagonized by clozapine, haloperidol, chlorpromazine, or pimozide. The stereoselectivity of this antagonism can be demonstrated with the optical enantiomers of sulpiride and butaclamol. This inhibitory effect of amphetamine on cholinergic neurotransmission appears to be the result of the stimulation of dopamine receptors of the D 2 subtype, as they were resistant to blockade by the preferential D 1 receptor antagonist SCH 23390. Inhibition of dopamine synthesis with α‐methyl‐ p ‐tyrosine antagonized the effects of amphetamine on [ 3 H]ACh release. The dopamine receptor‐mediated inhibition of the release of [ 3 H]ACh elicited at low frequencies of stimulation from rat striatal slices is a suitable model to test drugs that enhance dopaminergic neurotransmission. In addition, the antagonism of the inhibition of cholinergic neurotransmission by amphetamine in striatal slices represents a useful test for drugs with potential usefulness in clinical situations in which dopaminergic neurotransmission is exacerbated.