Functional antagonism of D-1 and D-2 dopaminergic mechanisms affecting striatal acetylcholine release

doi:10.1016/0024-3205(86)90577-1

Life Sciences

Volume 38, Issue 24, 16 June 1986, Pages 2247-2254

https://doi.org/10.1016/0024-3205(86)90577-1 Get rights and content

Abstract

Rat striatal slices prelabelled with [³H] choline were superfused with dopamine D-1 and D-2 agonists and antagonists, separately and in combination, during measurement of [³H]acetylcholine (ACh) release. SKF38393 (D-1 agonist), 10⁻⁷− 10⁻⁴M, and SCH23390 (D-1 antagonist), 10⁻⁷−10⁻⁵M, produced a dose-dependent increase in [³H]ACh release when given separately. The increased [³H]ACh release induced by either drug could not be attenuated by sufficient L-sulpiride to block D-2 receptors. yet both SKF38393, 10⁻⁶−10⁻⁵M, and SCH23390, 10⁻⁶−10⁻⁵M, were able to partially or fully overcome the [³H]ACh release-depressant effect of cosuperfused LY171555 (D-2 agonist), 10⁻⁶M. This suggests that a functional antagonism regarding striatal ACh release exists between D-1 and D-2 dopaminergic receptor-mediated mechanisms, but that D-1 modulation of local ACh release does not occur at the level of the recognition site of the striatal D-2 receptor. Finally, although attenuation of the increased release of striatal [³H]ACh induced by 10⁻⁵ SCH23390 by SKF38393 was seen, it is possible that such functional antagonism is not mediated by exclusively D-1 dopaminergic means.

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Cited by (28)

Regulation of dopamine D<inf>1</inf> and D<inf>2</inf> receptors on striatal acetylcholine release in rats
1997, Brain Research Bulletin
The effects of dopamine (DA) D₁ and D₂ receptors on striatal acetylcholine (ACh) releases were investigated by in vivo microdialysis. All drugs were applied via dialysis membrane directly to the striatum. The levels of ACh release were increased by 10⁻⁴ M SKF38393, a D₁ receptor agonist. Although 10⁻⁴ M SCH23390, a D₁ receptor antagonist, exhibited an increase in the levels of ACh release, the agonist (10⁻⁴ M) induced-increase in the levels of ACh release was suppressed by coperfusion of the antagonist (10⁻⁴ M). In contrast, the levels of ACh release were decreased by the D₂ receptor agonist, N-434, in a dose-dependent manner (10⁻⁵ M to 10⁻⁷ M) and increased by the D₂ receptor antagonist, sulpiride, in a dose-dependent manner (10⁻⁵ M to 10⁻⁷ M). The agonist (10⁻⁵ M) induced-decrease in the levels of ACh release was suppressed by coperfusion of the antagonist (10⁻⁶ M). Coperfusion of D₁ (10⁻⁴ M) and D₂ (10⁻⁵ M) agonists blocked both effects of respective drug alone. In order to clarify the effect of endogenous DA, two drugs with different mechanisms for enhancing DA concentration in the synaptic cleft, the DA release-inducer methamphetamine, and the DA uptake inhibitor nomifensine were perfused separately. Both (10⁻⁴ M to 10⁻⁶ M) produced a dose- and a time-dependent decrease in the levels of ACh release. Significant higher levels of ACh release were observed in the striatum of the 6-hydroxydopamine (8 μg/10 μl)-treated rats with significant depletion of striatal DA content. These results suggest that in striatal DA-ACh interaction ACh release, as cholinergic interneuron's activity, is tonically inhibited via the D₂ receptor, mainly by dopaminergic input, and the D₁ receptor probably modifies the effect of the D₂ receptor indirectly.
Differential localization of mRNAs encoding dopamine D<inf>1</inf> or D<inf>2</inf> receptors in cholinergic neurons in the core and shell of the rat nucleus accumbens
1995, Molecular Brain Research
By combining immunocytochemistry for ChAT and in situ hybridization for dopamine D₁ or D₂ receptor mRNA in the striatum, it was found that (1) the percentage of ChAT/D₂ mRNA co-localization is higher in the caudate-putamen than in the shell and core of the nucleus accumbens, (2) in the shell the degree of ChAT/D₂ mRNA co-localization is higher rostrally than caudally, and 3) no significant regional differences exist in the degree of co-localization of ChAT and D₁ mRNA.
Does dopamine exert a tonic inhibitory control on the release of striatal acetylcholine in vivo?
1994, European Journal of Pharmacology
The role of dopamine transmission on striatal acetylcholine release was investigated by using brain microdialysis. Blockade of dopamine D₂ receptors with (−)-sulpiride or haloperidol increased acethlcholine release to a maximum of 80% (after 50 and 0.5 mg/kg, respectively). This effect was prevented by blockade of dopamine D₁ receptors with 0.5 mg/kg SCH 39166 or 0.1 mg/kg SCH 23390, or by depletion of dopamine stores after 5 mg/kg reserpine + 150 mg/kg α-methyltyrosine. Treatment with SCH 39166, SCH 23390 or reserpine + α-methyltyrosine reduced acetylcholine release by about a maximum of 30%. Stimulation of dopamine D₂ receptors with LY 171555 (quinpirole) at a low, sedative dose (0.05 mg/kg) reduced acetylcholine release by about 30% with no further reduction at higher doses up to 1 mg/kg. Moreover, LY 171555 (0.1 mg/kg) given to SCH 39166 (0.5 mg/kg)- or SKF 38393 (20 mg/kg)-pretreated rats did not decrease acetylcholine release, suggesting that its effect is through a dopamine D₁ receptor-mediated mechanism. In contrast, in dopamine-depleted rats, LY 171555 0.1 mg/kg became more effective in decreasing acetylcholine release (about 70%) also after SCH 39166 (0.5 mg/kg) pretreatment (about 80%), thus acting independently of dopamine D₁ receptor mechanisms. These results indicate that, in normal circumtances, endogenous dopamine facilitates striatal acetylcholine release through dopamine D₁ receptors. The results argue against the commonly accepted view that dopamine D₂ receptors exert a tonic inhibitory control on acetylcholine release. Moreover, they suggest that dopamine D₂ receptors, in circumstances of dopamine depletion, may exert an inhibitory control on acetylcholine release independent of dopamine D₁ receptor mechanisms.
Increases in striatal acetylcholine by SKF-38393 are mediated through D<inf>1</inf> dopamine receptors in striatum and not the frontal cortex
1993, Brain Research
It has been proposed by some that the D₁ receptor effects are mediated through striatal actions while others have suggested that they are determined indirectly through the frontal cortex. The experiments reported here represent a further attempt to resolve this controversy. It was found that focal applications of the inactive and active enantiomers of SKF-38393 (a D₁ dopamine receptor agonist) to the rat striatum via reverse dialysis increased extracellular acetylcholine (ACh) in a stereoselective manner. Infusions of SKF-38393 into the frontal cortex, on the other hand, were ineffective in altering striatal ACh. Furthermore, partial hemisections caudal to the frontal cortex did not alter the ability of systemically administered SKF-38393 to increase striatal ACh. Taken together, these results suggest that at least some of the effects of D₁ receptor agonists on striatal cholinergic function are mediated through actions in the striatum and not the frontal cortex.
An investigation into the effects of apomorphine on the release of acetylcholine in the striatum of freely-moving rat using in vivo microdialysis
1993, General Pharmacology
- 1.
  1. Using in vivo microdialysis, we studied the effects of apomorphine on the release of acetylcholine (ACh) in the striatum of freely-moving rats.
- 2.
  2. Basal release of ACh was 3.01 ± 0.51 pmol/15 min in 30 μl (containing of 10 μM neostigmine) of the striatal perfusate.
- 3.
  3. Ringer containing tetrodotoxin (1 μM), hemicholinium-3 (5 mM), or Ca²⁺-free Ringer was perfused into the striatum. Each of these treatments produced a significant attenuation in release content of ACh. High K⁺ (30 mM) produced a significant increase in ACh release.
- 4.
  4. In normal rats, apomorphine (0.05 mg/kg, s.c.) increased striatal ACh release. A high dose (1.0 mg/kg) significantly attenuated release.
- 5.
  5. In 6-OHDA-pretreated rats, although the lower dose of apomorphine did not increase striatal ACh release, the high dose produced a more significant attenuation of release.
- 6.
  6. It is concluded that apomorphine enhanced or attenuated the striatal ACh release and that this effect was regulated by nigro-striatal dopaminergic system in the freely moving rats.
Effects of D<inf>1</inf> and D<inf>2</inf> antagonists on the transient increase of dopamine release by dopamine agonists by means of brain dialysis
1991, Neuroscience Letters
The effects of selective D₁ and D₂ antagonists, R-(+)-8-chloro-2,3,4,5,-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol (SCH-23390) and sulpiride, on the transient increase of dopamine (DA) release induced by DA agonists, apomorphine (APO) and 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (SKF-38393) were examined in the caudate-putamen of freely moving rat by means of microdialysis during local coinfusion of a DA antagonist and agonist. Infusion of 10⁻⁵ M and/or 10⁻⁶ M concentrations of SCH-23390 suppressed a brief increase in DA release induced by both 10⁻⁴ M of APO and 10⁻⁵ M of SKF-38393. On the other hand, 10⁻⁵ M and/or 10⁻⁶ M of sulpiride exerted little or no effect. A possible explanation for this phenomenon was discussed.

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Functional antagonism of D-1 and D-2 dopaminergic mechanisms affecting striatal acetylcholine release

Abstract

Life Sci.

Brain Res.

Life Sci.

Life Sci.

Europ. J. Pharmacol.

Europ. J. Pharmacol.

Europ. J. Pharmacol.