Biomedical subjects

J W Richard

Publications and source records attributed to J W Richard.

15 recordsLinked to original sources

PubMed1995

Local modulation of hippocampal acetylcholine release by dopamine D1 receptors: a combined receptor autoradiography and in vivo dialysis study.

The modulation of in vivo hippocampal ACh release by dopaminergic D1 and D2 receptors was examined in this study. Additionally, in an attempt to ascertain the location of these receptors in relation to hippocampal cholinergic terminals, fimbriaectomy and quantitative autoradiography were used. Following unilateral fimbriaectomy, whereby at least 50% of hippocampal cholineacetyltransferase (ChAT) activity was lost, a significant ipsilateral decrease in D1/3H SCH23390 binding was observed in the molecular layer of the dentate gyrus while hippocampal D2/3H raclopride binding was unaffected. The effects of prototypical D1 and D2 receptor agonists and antagonists on hippocampal ACh release were examined next using in vivo dialysis in freely moving rats. The D1 agonist SKF 38393 (10 microM to 100 microM) administered directly into the hippocampus via the dialysis probe stimulated ACh release in a concentration dependent manner. The effect of the agonist was blocked by the coadministration of the D1 receptor antagonist SCH 23390 (1 microM), which by itself failed to modulate ACh release. In contrast, neither the D2 agonist quinpirole (1-10 microM) nor the D2 antagonist sulpiride (1-10 microM) had any direct effect on hippocampal ACh release. Additionally, the infusion of these D1 and D2 drugs in the septal area failed to affect hippocampal ACh release. Taken together, these results suggest that a proportion of hippocampal D1 receptors are located on cholinergic nerve terminals and that dopamine, acting via D1 receptors, can locally stimulate hippocampal ACh release.

Acetylcholine↗

PubMed1991

Acetylcholine levels and choline acetyltransferase activity in rat cerebrovascular bed after uni- or bilateral sphenopalatine ganglionectomy.

Endogenous acetylcholine (ACh) levels and choline acetyltransferase (ChAT) activity were measured in several vascular segments (major cerebral arteries, cortical pial vessels, and peripheral arteries) and nervous tissues [including the sphenopalatine ganglion (SPG)] in the rat. The effects of uni- or bilateral surgical ablation of the SPG, a putative origin of the cholinergic cerebrovascular innervation, were investigated on these two specific cholinergic markers at various postoperative times. ChAT activity and ACh levels were enriched in the cerebral as compared to the peripheral arteries. Among the cerebrovascular tissues tested, ACh levels were particularly high in the circle of Willis and the vertebrobasilar segments and, to a lesser extent, in the middle cerebral artery. Lower levels were found in the small pial vessels and choroid plexus. Overall, ChAT activity measured in different arterial beds paralleled the distribution of ACh. Following uni- or bilateral removal of the SPG, slight reductions (18-36%, statistically not significant) were observed in ChAT activity in rostral cerebral arteries and pial vessels overlying the frontal cortex. Similarly, bilateral ganglionectomy resulted in minor decreases (11-22%, not significant) in the cerebrovascular contents of ACh in these same vascular segments. These results clearly show that the SPG does not or only partly contributes to the cholinergic fibers that supply the cerebrovascular bed.

Acetylcholine↗

PubMed1991

Suppression of in vivo neostriatal acetylcholine release by vesamicol: evidence for a functional role of vesamicol receptors in brain.

Experiments examined the effects of peripheral and central administration of the vesicular acetylcholine transport blocker vesamicol (AH5183) on the content, synthesis, and release of acetylcholine in the rat brain in vivo. In time course studies, a single intraperitoneal dose of DL-vesamicol (5 mg/kg) rapidly and reversibly (within 2 h) doubled the content of acetylcholine in the striatum and hippocampus, without affecting choline levels or the rate of transmitter synthesis. In microdialysis experiments, the same peripheral dose of drug produced a reversible 55% reduction in endogenous striatal acetylcholine release. A similar inhibitory effect was produced by direct intrastriatal perfusion with vesamicol. Moreover, this effect of vesamicol was (a) concentration-dependent and saturable (EC50 = 68 nM), (b) rapidly reversible, (c) stereospecific for the L-isomer, and (d) poorly mimicked by a vesamicol analog with lower plasma membrane permeability. This profile of effects is consistent with an interaction with a specific vesamicol receptor as defined by previous in vitro binding studies. These results support a functional role for vesamicol receptors in modulating central cholinergic transmission in vivo.

Acetylcholine↗

PubMed1990

Drug effects on the release of endogenous acetylcholine in vivo: measurement by intracerebral dialysis and gas chromatography-mass spectrometry.

Intracerebral microdialysis was combined with a sensitive and specific gas chromatographic-mass spectrometric assay to measure the release of endogenous acetylcholine in the rat striatum in vivo. In rats anesthetized with urethane (1.2 g/kg i.p.), the levels of striatal acetylcholine dialyzed into a Ringer's perfusate were: (a) reliably measurable only in the presence of physostigmine; (b) stable at between 3 and 8 h of perfusion (30-75 pmol/20 min in the presence of 75 microM physostigmine); (c) reduced by calcium-free Ringer's solution, tetrodotoxin (0.1 microM), and vesamicol (1.0 microM); and (d) increased by elevated potassium (100 mM), atropine (3-300 microM), and haloperidol (0.75 mg/kg i.p.). In conscious unrestrained rats, the spontaneous release of striatal acetylcholine was not altered significantly following the administration of urethane. The changes in acetylcholine release observed in this study are consistent with the known actions of some drugs or ionic conditions on striatal cholinergic neurotransmission and are evident under the condition of urethane anesthesia. The present results demonstrate the sensitivity and suitability of this method for monitoring endogenous striatal acetylcholine release in vivo.

Acetylcholine↗

PubMed1985

Some factors affecting striatal 3-methoxytyramine concentrations in the mouse and rat.

Apomorphine, a DA agonist, at a dose of 2 mg/kg, produced a rapid decline in 3-MT concentrations in the rat striatum; this is consistent with a reduction in the firing rate of nigrostriatal neurons. The injection of a 12.5 mg/kg dose of phenylethylamine transiently increased 3-MT concentrations in the mouse striatum. A more profound increase was produced by this dose in the rat striatum. Cocaine (5 mg/kg) produced a decrease in DOPAC concentrations in both species thus suggesting that the re-uptake of DA from the synaptic cleft in both species was very similar. Amfonelic acid, however, produced a different profile in each species. The concentration of 3-MT is larger in the mouse striatum as a result of several possible mechanisms: the higher percentage of MAO isoenzyme B in the mouse brain (3-MT is a preferred substrate of MAO isoenzyme A) and/or due to differences in the clearance mechanisms for 3-MT produced extraneuronally - with the mouse having a less avid clearance system either for DA or for 3-MT.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1983

Agonist/antagonist analgesics and nigrostriatal dopamine metabolism in the rat: evidence for receptor dualism.

Agonist/antagonist (Ag/Ant) analgesics possess bell-shaped dose-response curves with regard to nigrostriatal dopamine (DA) metabolism in the rat. Using local drug injections as well as parenteral drug, after acute hemisection, we have determined that this phenomenon is not the result of autoinhibition. Our data clearly indicate that the receptor population antagonizing the agonist actions of Ag/Ant is not localized within the striatum or substantia nigra. These results therefore present evidence for receptor dualism with Ag/Ant analgesics.

Animals↗

PubMed1983

Multiple opiate receptor affinities of kappa and agonist/antagonist analgesics: in vivo assessment.

The affinities of kappa and agonist/antagonist (Ag/Ant) analgesics for mu and delta opiate receptors were examined in vivo in the rat. In the case of kappa agonists, these agents appear to be mu and delta antagonists in vivo. The mu antagonist activity appears to involve a specific isoreceptor population, namely mu-2 receptors. With Ag/Ant analgesics, a more complex pharmacology is evident such that at mu and delta receptor populations these agents can exhibit pure Ag, pure Ant or a combination of Ag and Ant actions. These activities vary with the neuronal localization of the receptor population being examined. In addition, complex species differences are evident with Ag/Ant actions.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1982

Antagonists of excitatory amino acids and cyclic guanosine monophosphate in cerebellum.

The excitatory amino acid analogues kainate, quisqualate, domoic acid, 4-fluoroglutamate, homocysteic acid and N-methylaspartate as well as the tremor-inducing drugs harmaline and oxotremorine all induced significant elevations in cyclic guanosine monophosphate (cGMP) levels in the cerebellum in vivo. The putative antagonists of excitatory amino acids, 2-amino-5-phosphonovalerate (APV) and piperidine dicarboxylate (PDA) both blocked the actions of the tremorogens. Piperidine dicarboxylate also blocked the in vivo activity of all the amino acid analogues except homocysteic acid and N-methylaspartate. 2-Amino-5-phosphonovalerate (APV) was inactive against kainate, quisqualate and homocysteic acid. It therefore appears that PDA and APV are useful tools for the further study of the function of glutamate and asparatate receptors.

2-Amino-5-phosphonovalerate↗

PubMed1982

Morphine and nigrostriatal function in the rat and mouse: the role of nigral and striatal opiate receptors.

Using local injections of drugs and hemisection experiments, a comparison was made of the actions of morphine on the dopaminergic nigrostriatal system of the rat and mouse. In the rat, morphine appeared to act exclusively at presynaptic opiate receptors on dopaminergic nerve endings in the striatum. Activation of these receptors resulted in enhanced dopamine synthesis but with no associated increase in dopamine release. In the mouse, morphine acted at the level of the substantia nigra to enhance both striatal dopamine synthesis and release. The exact localization of these receptors in the substantia nigra remains to be determined.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1980