The Inhibition of the Conditioned Response and the Counteraction of Schizophrenia by Muscarinic Stimulation of the Brain

Pfeiffer, Carl C.; Jenney, Elizabeth H.

doi:10.1111/j.1749-6632.1957.tb40764.x

Cited by 187 publications

(55 citation statements)

References 13 publications

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“…The failure in acquisition of DB by MA in 4 experiments would also be the result of increased alertness since programs on acquisition of DB in these 4 experiments were more complicated and included aversive stimuli. Although several studies have indicated that physostigmine inhibited the performance of conditioned avoidance behaviour (13,14,15), smaller doses of physostigmine has been shown to enhance discrimination learning (16,17,18,19,20). In every experiment herein, ES produced no significant changes in the acquisition of DB.…”

Section: Discussionmentioning

confidence: 75%

Effects of panax ginseng root on acquisition of sound discrimination behaviour in rats

Saito

Tsuchiya

Naka

et al. 1979

Japanese Journal of Pharmacology

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Abstract-Pole-climbing and shuttle-avoidance tests were employed to study the acquisition of conditioned avoidance response (CAR) and discrimination behaviour (DB) in male Wistar rats which had been given extracts from Panax Ginseng root intraperitoneally or orally. Neither a lipid soluble fraction (GNo. 5) nor a ginsenoside Rg fraction (GRg) produced significant changes in the acquisition of CAR. GRg given intraperitoneally produced a significant acceleration in the acquisition of DB between a 500 Hz signal sound followed by an electric shock (SD) and a 1000 Hz signal sound without a shock (SJ) in rats which had learned to avoid the shock following S1 at a rate of over 95 %. Small doses of GNo. 5 produced a significant depression in the acquisition of DB. MATERIALS AND METHODS 1) Pole-Climbing TestThe experimental details of the apparatus and the procedure of training were as reported in our previous report (6).

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Section: Discussionmentioning

confidence: 75%

Effects of panax ginseng root on acquisition of sound discrimination behaviour in rats

Saito

Tsuchiya

Naka

et al. 1979

Japanese Journal of Pharmacology

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“…It is possible that the muscarinic partial agonist activity also contributes to the antipsychotic profile of clozapine, a drug effective in treating both positive and negative symptoms of schizophrenia (Meltzer, 1995). Indeed, there are reports that the stimulation of central muscarinic receptors has beneficial effects in schizophrenia, especially on positive symptoms refractory to conventional treatment (Pfeiffer and Jenney 1957;Rosenthal and Bigelow 1973). The intrinsic muscarinic activity of clozapine may contribute to the clinical utility of the drug in improving this symptomatology.…”

Section: Discussionmentioning

confidence: 99%

Mixed Agonist–Antagonist Properties of Clozapine at Different Human Cloned Muscarinic Receptor Subtypes Expressed in Chinese Hamster Ovary Cells

Olianas

Maullu

Onali

1999

Neuropsychopharmacology

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“…Pfeiffer and Jenney (1957) administered the cholinomimetic compound arecoline by subcutaneous injection to 23 schizophrenic patients and clinical improvement described as 'lucid intervals' was reported in more than 80% of the patients. However, potent parasympatomimetic side effects confound the clinical use of nonselective cholinergic receptor agonists.…”

Section: Introductionmentioning

confidence: 99%

The Muscarinic M1/M4 Receptor Agonist Xanomeline Exhibits Antipsychotic-Like Activity in Cebus apella Monkeys

Andersen

Fink-Jensen

Peacock

et al. 2003

Neuropsychopharmacol

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Xanomeline is a muscarinic M 1 /M 4 preferring receptor agonist with little or no affinity for dopamine receptors. The compound reduces psychotic-like symptoms in patients with Alzheimer's disease and exhibits an antipsychotic-like profile in rodents without inducing extrapyramidal side effects (EPS) at therapeutically relevant doses. In the present study, we examined whether the xanomeline-induced functional dopamine antagonism found in rodent studies could also be observed in nonhuman primates. In addition, we studied whether the lack of EPS observed in rodents also applies to primates. To this end, we investigated the effects of xanomeline on the behavior induced by D-amphetamine and (À)-apomorphine in drug-naive Cebus apella monkeys. Antipsychotic compounds antagonize amphetamine-induced motor unrest and stereotypies in this species. Xanomeline inhibited D-amphetamine-induced motor unrest, stereotypies and arousal as well as apomorphine-induced stereotypies and arousal in drug-naive Cebus apella monkeys. Xanomeline did not induce EPS but vomiting occurred in some monkeys at high doses, in accordance with emetic events observed in Alzheimer patients following xanomeline administration. Even when xanomeline was tested in EPS-sensitized Cebus apella monkeys, EPS were not observed at the dose range of xanomeline used in the D-amphetamine-apomorphine combination study (0.5-3 mg/kg). However, when xanomeline was tested at 4 mg/kg, moderate dystonia was seen in two out of three monkeys. It is concluded that xanomeline inhibits Damphetamine-and (À)-apomorphine-induced behavior in Cebus apella monkeys at doses that do not cause EPS. These data further substantiate that muscarinic receptor agonists may be useful in the pharmacological treatment of psychosis.

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The Inhibition of the Conditioned Response and the Counteraction of Schizophrenia by Muscarinic Stimulation of the Brain

Cited by 187 publications

References 13 publications

Effects of panax ginseng root on acquisition of sound discrimination behaviour in rats

Effects of panax ginseng root on acquisition of sound discrimination behaviour in rats

Mixed Agonist–Antagonist Properties of Clozapine at Different Human Cloned Muscarinic Receptor Subtypes Expressed in Chinese Hamster Ovary Cells

The Muscarinic M1/M4 Receptor Agonist Xanomeline Exhibits Antipsychotic-Like Activity in Cebus apella Monkeys

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