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D L Cheney

Publications and source records attributed to D L Cheney.

At least 91 records · Page 5Linked to original sources
PubMed1976

Correlation between analgesia and the decrease of acetylcholine turnover rate in cortex and hippocampus elicited by morphine, meperidine, viminol R2 and azidomorphine.

In rats, an ED50 for analgesia of morphine, meperidine, viminol R2 or azidomorphine decreases the turnover rate of acetylcholine (TRACh) in cortex and hippocampus. These four analgetics fail to change to TRACh in striatum when given in a dose range from ED30 for analgesia up to a cataleptic dose. Viminol S2, a nonanalgesic stereoisomer of vimonol R2, fails to decrease the TRACh in cortex and hippocampus. Naltrexone, an opiate antagonist, also fails to change the cortical and hippocampal TRACh but it antagonizes the decrease in cortical and hippocampal TRACh elicited by the four analgetics. Since the ED50 of these four analgetics fails to change the TRACh in striatum which contains a high density of opiate receptors and intrinsic cholinergic neurons, but decreases the TRACh in hippocampus and cortex which contain a low density of opiate receptors, it can be inferred that opiate receptors are not exclusively involved in the regulation of TRACh. However, the results suggest that certain cholinergic pathways participate in the mediation of analgesia.

Acetylcholine↗
PubMed1976

In vivo actions of clozapine and haloperidol on the turnover rate of acetylcholine in rat striatum.

We have measured acetylcholine (ACh) content and turnover rate (TRACh) in striatum and cortex of rats receiving haloperidol and clozapine i.p. Both clozapine (30 mumol/kg) and haloperidol (10 mumol/kg) reverse the decrease in striatal TRACh elicited by apomorphine (11 mumol/kg) while each antipsychotic affects the steady state and the TRACh in striatum differently. Haloperidol fails to change striatal ACh content but increases the TRACh; chozapine (15 and 30 mumol/kg) neither decreases the content of ACh nor changes the TRACh in striatum. Moreover, 60 or 90 mumol/kg of clozapine causes a 40% decrease in ACh content without affecting the TRACh. Clozapine, but not haloperidol, antagonizes the increase in ACh content and the decrease in TRACh elicited by arecoline (64 mumol/kg) and oxotremorine (9 mumol/kg) in striatum. Clozapine resembles trihexylphenidyl (14 mumol/kg) and benztropine (12 mumol/kg) because it decreases the ACh content of striatum without changing the TRACh. Moreover, clozapine and benztropine reverse the increase in striatal TRACh elicited by haloperidol. The increase in striatal TRACh elicited by haloperidol could be of value to explain the extrapyramidal action of this drug. The anticholinergic action of clozapine could explain the absence of extrapyramidal side effects observed with this drug.

Animals↗
PubMed1975

Steady-state concentrations of choline and acetylcholine in rat brain parts during a constant rate infusion of deuterated choline.

An intravenous infusion of deuterated choline at constant rate for 6 min (5 or 25 mumoles kg-1 min-1) significantly increases the concentration of choline in plasma, occipital cortex and striatum. Both 5 and 25 mumoles kg-1 min-1 increase the concentration of acetylcholine in cortex but only 25 mumoles kg-1 min-1 increases the acetylcholine content in striatum. In contrast, 1 mumole kg-1 min-1 does not change the choline or acetylcholine content in cortex or striatum. A single pulse injection of choline (200 mumoles kg-1) causes a significant increase in the concentration of choline in striatum 30 sec following injection. The choline content returns to normal values within 2 min. These studies show that when a pulse injection of a non-tracer dose of radioactive choline is used to measure brain acetylcholine turnover rate the maintenance of steady state must be verified within seconds after the pulse injection of radioactive choline. When constant infusion of deuterated choline is used to measure turnover rate of acetylcholine in the brain of rats, a dose of 1 mumole kg-1 min-1 appears to be a maximal infusion rate.

Acetylcholine↗
PubMed1975

Application of principles of steady-state kinetics to the in vivo estimation of acetylcholine turnover rate in mouse brain.

The rate of metabolism of acetylcholine (ACh) in mouse brain in vivo has been estimated utilizing a radio gas chromatographic approach and pulse labeling with radioactive phosphorylcholine. A kinetic model describing the change with time of the plasma choline (Ch), brain Ch and ACh specific radioactivities as interdependent variables is postulated. The experimental results are analyzed kinetically according to this model using two methods: the finite difference method described by Neff et al. (J. Pharmacol. Exp. Ther. 176: 701-710, 1971) and a simple graphic method based on the transformation of the data in terms of the decline of plasma Ch radioactivity described in this paper. The accuracy of the latter is evaluated by the classic method of the least mean squares. Calculations with the two methods yield comparable results. This method is simple and can be used to study drug effects on brain ACh turnover rate. ACh turnover rate in mouse brain has been calculated to be 0.36 mumol/g/hr with the latter method, whereas the finite difference method yields slightly lower values. Because of the compartmentalization of brain Ch and the inherent assumptions, the new method can be used only for data collected during the exponential decline of plasma radioactive choline.

Acetylcholine↗
PubMed1975

Application of principles of steady-state kinetics to the estimation of brain acetylcholine turnover rate: effects of oxotremorine and physostigmine.

We have measured the turnover rate of acetylcholine (ACh) in the brains of mice injected with doses of oxotremorine and physostigmine that cause a prolonged increase of ACh concentration in brain. The method used to measure turnover rate of ACh is an application of principles of steady-state kinetics to the change with time of brain choline (Ch) and ACh specific radioactivities after an intravenous pulse injection of phosphorylcholine. We have found that when the concentration of brain ACh and Ch is increased to a new steady state as a result of oxotremorine and physostigmine injections the turnover rate of brain ACh decreases from 0.34 mumol/g/hr (in saline-treated mice) to 0.12 and 0.061 mumol/g/hr, respectively. The possibility that an increase of brain Ch or ACh concentrations plays a role in the control of brain ACh turnover rate is discussed.

Acetylcholine↗
PubMed1975

Morphine dependence and in vivo turnover of acetylcholine in whole mouse brain.

Turnover rates of acetylcholine (ACh) were estimated in mouse brain after intravenous injection of phosphoryl(Me-14C)choline by applying principles of steady-state kinetics to the change with time of choline and ACh specific radioactivities. Turnover rate of brain ACh was estimated: 1) 45 minutes after a single injection of morphine (350 mumol/kg); 2) 3.5 days after implantation of a morphine pellet (250 mumol/pellet); 3) 15 minutes after 24 mumol/kg of naloxone to precipitate withdrawal in mice implanted with morphine pellets for 3.5 days; and 4) 15 minutes after 24 mumol/kg of naloxone. Brain ACh turnover rate was unchanged in mice that were given a single injection of morphine but was increased significantly in mice that had been made physically dependent upon morphine. During naloxone-precipitated withdrawal, the brain ACh turnover rate was found to be equal to that of mice treated only with naloxone.

Acetylcholine↗