Regulation Of Striatal Acetylcholine Release Research Articles

In vitro evidence for increased facilitation of striatal acetylcholine release via pre- and postsynaptic NMDA receptors in hemiparkinsonian rats.

The NMDA-evoked acetylcholine release from striatal slices and synaptosomes was investigated in rats subjected to unilateral injection of 6-hydroxydopamine into the substantia nigra. In slices prepared from the striatum contralateral to the lesion, the NMDA-evoked endogenous acetylcholine release was not significant at 10 microM NMDA and maximal at 100 microM NMDA (124 +/- 19%). Conversely, in slices taken from the dopamine-depleted striatum, NMDA was effective even at 10 microM (41 +/- 4%), and at 100 microM (196 +/- 24%) efficacy was nearly doubled. In synaptosomes prepared from the contralateral striatum, NMDA maximally stimulated 20 mM KCl-induced endogenous acetylcholine release at 1 microM (66 +/- 5.1%), with lower concentrations (0.01-0.1 microM) being ineffective. Conversely, in synaptosomes prepared from the dopamine-depleted striatum, NMDA maximally enhanced the K+/--evoked acetylcholine release at 0.1 microM (118 +/- 12.4%). Concentration-response curves of NMDA-evoked acetylcholine release in sham-operated rats could be superimposed on those observed in the contralateral striatum of the 6-hydroxydopamine-lesioned animals. The present data support the view of an increased glutamatergic regulation of striatal acetylcholine release via pre- and postsynaptic NMDA receptors during Parkinson's disease.

Dopaminergic regulation of striatal acetylcholine release: the critical role of acetylcholinesterase inhibition.

This study examined the effects of different levels of acetylcholinesterase (AChE) inhibition on dopaminergic regulation of striatal acetylcholine (ACh) release as estimated by in vivo brain microdialysis. Systemic administration of d-amphetamine (2 or 10 mg/kg) increased the striatal output of ACh when the AChE inhibitor neostigmine (0.1 microM) was present in the perfusion fluid. In contrast, when the same experiments were conducted at 0.01 microM neostigmine, d-amphetamine failed to affect (2 mg/kg) or significantly decreased (10 mg/kg) striatal ACh output. The inhibitory action of the D2 receptor agonist quinpirole (0.2 mg/kg) was significantly greater at 0.01 microM than at 0.1 microM neostigmine. Similarly, there was a nonsignificant trend for the D2 antagonist raclopride (1 mg/kg) to stimulate ACh release to a greater extent at the low neostigmine concentration. In contrast, the stimulant effects of systemic administration of the D1 agonist A-77636 (1.46 mg/kg) on striatal ACh release were the same at the two neostigmine concentrations. These results demonstrate that the concentration of an AChE inhibitor in the perfusion solution can quantitatively and even qualitatively influence the manner in which dopaminergic agents regulate ACh overflow in the striatum. On comparing the present results with earlier reports concerning the effects of d-amphetamine on tissue concentrations of ACh, it is tentatively concluded that a low neostigmine concentration is the more physiologically relevant condition. Under such conditions, at moderate doses d-amphetamine does not appear to alter striatal ACh release, with this likely being due to the opposing actions of D1 and D2 receptors. Nevertheless, until the endogenous interstitial concentrations of striatal ACh can be measured by other methods, the physiological relevance of ACh microdialysis studies in the striatum will remain uncertain.

O-83 - The role of nitric oxide in the regulation of striatal acetylcholine release induced by N-methyl-D-aspartate

O-83 - The role of nitric oxide in the regulation of striatal acetylcholine release induced by N-methyl-D-aspartate

Augmented pharmacologic stimulation of striatal acetylcholine release following developmental hypoxic-ischemic injury

We have previously shown that developmental hypoxic-ischemic injury in a unilateral rodent model leads to an increase in both morphologic and biochemical indices of striatal cholinergic neurons. To investigate the functional significance these changes, we have used the in vivo microdialysis technique to examine the regulation of striatal acetylcholine release in awake, adult rats following postnatal hypoxic-ischemic injury. We have found that injury does not alter basal release of acetylcholine, but it results in a marked augmentation in the increase of acetylcholine release normally observed after infusion of atropine or pirenzepine.

The effect of intrastriatal application of directly and indirectly acting dopamine agonists and antagonists on the in vivo release of acetylcholine measured by brain microdialysis. The importance of the post-surgery interval.

The effect of intrastriatal application of D-1, D-2 and indirect dopaminergic drugs on the release of striatal acetylcholine as a function of the post-implantation intervals was studied using in vivo microdialysis. The dopamine D-2 agonists LY 171555 and (-)N0437 inhibited the release of striatal acetylcholine to 40% of control values 16-24 h after implantation of the dialysis cannula. When LY 171555 was infused 40-48 h after implantation of the dialysis cannula, the response was attenuated to 20% of control values. Meanwhile, the effectiveness of infusions of the antagonists (-)sulpiride and haloperidol was augmented from a non significant effect at 16-24 h to a 150% increase 40-48 h after implantation of the cannula. Infusions of the dopamine releasing agent amphetamine or the dopamine uptake inhibitor nomifensine resulted in a dose-dependent increase in the overflow of dopamine. Not until a sevenfold increase in the level of dopamine was seen, the release of acetylcholine was significantly affected. This hyporesponsiveness of the striatal cholinergic interneurons to endogenous dopamine could not be attributed to dopamine D-1 receptor activation, since no effects on striatal acetylcholine release were found by intrastriatal infusions of the selective D-1 agonist CY 208-243 or the selective D-1 antagonist SCH 23390. The results indicate that dopamine D-2 receptors are involved in the regulation of striatal acetylcholine release and that these receptors are tonically occupied by endogenous dopamine under the present experimental conditions 40-48 h after probe implantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Dopamine D 1 receptor stimulation increases striatal acetylcholine release in the rat

The effect of selective D 1 receptor agonists on acetylcholine (ACh) release in the striatum was investigated using in vivo microdialysis. Administration of the reactive enantiomer, (+)-SKF 38393 (2, 10 mg/kg s.c.), doses which elevate grooming and sniffing behaviour, increased ACh release by 40 and 75%, respectively. Another D 1 receptor agonist CY 204–283 (1 mg/kg s.c.) also produced a 75% increase in ACh output. The racemate (±)-SKF 38393 (20 mg/kg s.c.) increased ACh output by 60% and this was completely blocked by the D 1 receptor antagonist SCH 23390 (0.3 mg/kg s.c.). In contrast, administration of the D 2 receptor antagonist raclopride (1 mg/kg s.c.), 60 min after (±)-SKF 38393 (20 mg/kg s.c.), further increased ACh release. These results suggest that activation of D 1 receptors increases ACh release in vivo and that D 1 and D 2 receptors have opposing roles in the regulation of striatal ACh release.

Regulation of Striatal Acetylcholine Release by Dopamine after Nigrostriatal Bundle Injury

Annals of the New York Academy of SciencesVolume 604, Issue 1 p. 606-608 Regulation of Striatal Acetylcholine Release by Dopamine after Nigrostriatal Bundle Injury DENISE JACKSON, DENISE JACKSON Department of Behavioral Neuroscience Center for Neuroscience University of Pittsburgh Pittsburgh, Pennsylvania 15260Search for more papers by this authorMICHAEL J. ZIGMOND, MICHAEL J. ZIGMOND Department of Behavioral Neuroscience Center for Neuroscience University of Pittsburgh Pittsburgh, Pennsylvania 15260Search for more papers by this author DENISE JACKSON, DENISE JACKSON Department of Behavioral Neuroscience Center for Neuroscience University of Pittsburgh Pittsburgh, Pennsylvania 15260Search for more papers by this authorMICHAEL J. ZIGMOND, MICHAEL J. ZIGMOND Department of Behavioral Neuroscience Center for Neuroscience University of Pittsburgh Pittsburgh, Pennsylvania 15260Search for more papers by this author First published: August 1990 https://doi.org/10.1111/j.1749-6632.1990.tb32039.xCitations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume604, Issue1Presynaptic Receptors and the Question of Autoregulation of Neurotransmitter ReleaseAugust 1990Pages 606-608 RelatedInformation

Pharmacologic evidence for direct dopaminergic regulation of striatal acetylcholine release

This study was done to provide pharmacologic evidence for the location of those striatal dopamine D-1 and D-2 receptors that participate in the regulation of local acetylcholine (ACh) release. Striatal tissue slices from adult male Sprague-Dawley rats were preloaded with [ 3H]choline and superfused in separate experiments with buffer containing either: (1) a D-2-specific agonist (LY141865 or LY171555), (2) a D-2 specific antagonist (L-sulpiride), (3) a D-1 specific agonist (SKF38393), or (4) a D-1 antagonist (SCH23390), in the presence or absence of tetrodotoxin (TTX), used to block interneuronal activity. With either D-2 agonist there was a dose-dependendent decrease in K +-stimulated [ 3H]ACh release, maximally at 5×10 −7 − 10 −6M [agonist] and to the same extent with each drug. Both SKF38393 and SCH23390 increased [ 3H]ACh release at tested concentrations of these agents. Results were unchanged when any of the drugs used was superfused in the presence of TTX, 5×10 −7M. These data are consistent with the hypothesis that populations of striatal D-1 and D-2 receptors exist on local cholinergic neurons, where they regulate ACh release. Alternative interpretations are discussed.