Role of N-methyl-d-aspartic acid and cholecystokinin receptors in apomorphine-induced aggressive behaviour in rats (original) (raw)
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Modification of apomorphine induced aggression by changing central cholinergic activity in rats
Neuropharmacology, 1977
ABSTRACT The aggression produced in groups of rats by apomorphine was dose-dependently antagonized by the cholinergic agonist, pilocarpine and intensified by the anticholinergic, dexetimide. The pilocarpine effect was evident even when its peripheral actions were blocked by isopropamide. The possible importance of a dopaminergic-cholinergic interaction in drug-induced aggression is discussed.
Behavioral effects of apomorphine and diisobutyrylapomorphine in the mouse
Psychopharmacology, 1977
Stereotyped climbing and clinging responses of the mouse to apomorphine or its ester prodrug, O,O'-diisobutyrylapomorphine were evaluated. Acute doses of the ester up to 0.3 mmoles/kg were tolerated without apparent ill effects. Both aporphines produced dose-dependent behavioral responses that were blocked by neuroleptics. The duration of action of the ester was much greater than that of apomorphine. When maximal initial behavior during the first hour was evaluated, low equimolar doses of apomorphine and the ester were similar in potency; in contrast, the total behavioral response to larger closes of the ester was greater than to apomorphine, evidently reflecting the greater duration of action of the ester. Behavioral responses to both agents during the first hour decreased at doses above 0.1 mmoles/kg. Oxidized or O-methylated apomorphine did not antagonize the behavioral effects of apomorphine. Systemic injection of apomorphine or diisobutyrylapomorphine led to detectable levels of free apomorphine as estimated by a sensitive and selective fluorimetric assay. The timecourse and magnitude of the behavioral effects of both agents corresponded closely with brain levels of apomorphine. Apomorphine and dopamine (but not diisobutyrylapomorphine) stimulated adenylate cyclase activity in mouse striatal homogenates-an effect antagonized by neuroleptic drugs but not propranolol. Apomorphine exerted a biphasic effect on the cyclase in vitro and increased cyclic AMP levels in the striatum in vivo. The prolonged activity of apomorphine esters as depot prodrug agonists of putative dopaminergic mechanisms in the brain may provide clinically desirable characteristics.
Pharmacology Biochemistry and Behavior, 1976
Both morphine and the neuroleptics, haloperidol and oxyperomide, dose-dependently reduce the aggression in rats produced by 20 mg/kg of apomorphine, a dopamine receptor stimulant. The narcotics antagonist, naloxone, prevents this effect of morphine but not the effect of neuroleptics. Dexetimide, a centrally acting antimuscarnic drug, antagonizes the reduction in aggression produced by the neuroleptics, but does not affect morphine's action. The cholinergic agonist, pilocarpine, enhances this action of oxyperomide. These results suggest that a cholinergic component contributes to the anti-agression action of neuroleptics and demonstrates a difference in the mechanism of action between neuroleptics and morphine.
Analysis of the difference in the behavioral effects of apomorphine in C57BL/6 and DBA/2 mice
Pharmacology Biochemistry and Behavior, 1982
VETULANI, J., M. SANSONE AND A. OLIVERIO. Analysis of the difference in the behavioral effects of apomorphine in C57BL/6 and DBA/2 mice. PHARMAC. BIOCHEM. BEHAV. 17(5) 967-971, 1982.--The influence of pimozide on the effects of apomorphine on locomotor activity and stereotypy was studied in two inbred strains of mice. In C57BL/6 mice, in which apomorphine did not produce stereotypy of gnawing, the biphasic effect of apomorphine on locomotor activity (hypomotility followed by hypermotility) was unaffected by pimozide. In DBA/2 mice, in which high doses of apomorphine produce hypomotility and compulsive gnawing, both these effects (but not hypomotility produced by low doses of apomorphine) were counteracted by pimozide. The results are consistent with the assumption that both strains of mice have separate inhibitory and stimulatory dopamine receptors mediating locomotor activity. In addition, DBA/2 but not C57BL/6 mice have dopamine receptors which mediate stereotypy and are sensitive to pimozide.
PubMed, 2018
Psychostimulants substances, some of which are abused by humans, are generally believed to produce sensitization effects when they are repeatedly administered to animals. Apomorphine, a non-narcotic derivative of morphine, having agonistic property for dopamine in order to produce psycho stimulant-like effects. Meanwhile, chronic administration leads to behavioral sensitization. Therefore, present study destine to produce desensitization in animals by the repeated administration of tryptophan (100 mg/kg), thereafter treated with apomorphine (1.0 mg/kg) to observe the intensity of sensitization in rats pre-treated with tryptophan. Apomorphine on acute administration known to increase motor activity whereas repeated treatment of apomorphine initiates the sensitization of motor behavior. It is expected that the intensity of apomorphine induced sensitization would be affected in tryptophan-treated rats. Present study provide the clear-cut evidence that chronic treatment of apomorphine arouses the motor behavior of animals in both novel and anxiolytic model over the saline treated animals, whereas hypo locomotive behavior was seen in animals pre-treated with tryptophan, provides the evidence that preliminary treatment of tryptophan perturbs the apomorphine induced sensitization in animals. The discoveries present an inventive methodology for amplifying the remedial utilization of apomorphine and traditional psychostimulants.
Synapse, 1993
Previous research has revealed a role of repeated D, dopamine receptor stimulation in the development of behavioral sensitization to the DID, agonist apomorphine. The present experiments assessed the role of repeated D, receptor stimulation in neurochemical changes accompanying locomotor sensitization to apomorphine. To assess direct effects of D, stimulation on dopamine synthesis, rats were injected with the D, agonist SKF 38393 (8 mgkg), followed by a n injection with the 3,4-dihydroxyphenylalanine (DOPA) decarboxylase inhibitor, NSD-1015. DOPA accumulation, assessed in striatal, nucleus accumbens-olfactory tubercle (NAOT), and ventral mesencephalon (VM) tissue samples, was not affected by acute SKI? 38393. In the second experiment, rats were treated with 10 daily injections of vehicle, apomorphine (5 mg/kg) or the D, agonist SKF 38393 (8 or 16 mgkg). Daily measures of locomotor activity demonstrated a progressive increase in the apomorphine-treated rats, but not the SKI? 38393-treated rats, across the 10 days. On day 11, all rats were injected with NSD-1015 for measurement of DOPA accumulation. Dopamine synthesis was enhanced in the striatum after repeated apomorphine treatment. In contrast, repeated SKF 38393 treatment resulted in either a small decrease or no change in DOPA accumulation in the different brain regions (striatum, NAOT, VM). In the third experiment, tissue levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and L3H1SCH 23390 binding to D, receptors were measured in rats treated with 10 daily injections of vehicle, apomorphine (5 mgkg), or SKF 38393 (16 mgkg). In the striatum and NAOT, none of the repeated drug treatments had an effect on DOPAC or dopamine levels. In the VM, DOPAC levels were enhanced following repeated apomorphine, but not repeated SKF 38393, whereas dopamine levels were not affected by either drug treatment. D, binding was not altered by the repeated drug treatments. Since repeated D, stimulation by SKI? 38393 did not produce the same alterations in dopamine synthesis and DOPAC levels as repeated apomorphine, the neurochemical effects accompanying locomotor sensitization to apomorphine probably are not mediated by D, receptors. 8 1993 Wiley-Liss, Inc.
Prolonged apomorphine-like behavioural effects of apomorphine esters
Neuropharmacology, 1976
In vitro and in uiuo activities of a series of O,O'-diesters of apomorphine, including diacetyl-, dipropionyl-, diisobutyryl-, dipivaloyl-, and dibenzoylapomorphine, were evaluated in the rat. All esters provoked stereotyped gnawing behaviour in intact rats, as well as rotation in a direction contralateral to unilateral electrolytic lesions in the nigrostriatal pathway. The esters were somewhat less potent than apomorphine in inducing these behavioural responses, and had a delayed latency to maximal effect as well as a prolonged duration of action. Prolongation of the behavioural effects of the esters increased with the size of the ester substituent, the dibenzoyl ester being 5 or 6 times longer-acting than apomorphine at high doses. Acute intraperitoneal doses of all esters, up to 100 mg/kg, were well tolerated. The behavioural activity of the esters after intragastric administration was poor. None of these esters increased the synthesis of cyclic AMP in striatal homogenates exhibiting adenylate cyclase activity stimulated by apomorphine or dopamine, and the smaller esters appeared to inhibit stimulation by dopamine. We conclude that the desirable prolongation of action of labile esteric derivatives of apomorphine is probably due to their increased lipophilic properties or to slow hydrolysis of the larger esters that converts the depot "pro-drugs" to the probable active product, apomorphine. This characteristic of esteric derivatives of apomorphine may provide a strategy for the design of improved, clinically useful agents that interact with central dopamine receptors.
Pharmacology & Toxicology, 1987
The effects of the novel substituted benzamide remoxipride on apomorphine induced behaviour in rats was investigated by means of an automatic holeboard apparatus. The ability of remoxipride to antagonise locomotion and gnawing induced by a high dose of apomorphine (5 mg/kg) and inhibition of exploration induced by a low dose of apomorphine (0.05 mg/kg) was tested. It was found that remoxipride in moderate doses potentiate locomotion and inhibit gnawing induced by the high dose of apomorphine while higher doses of remoxipride inhibits both apomorphine induced gnawing and locomotion. The inhibition of exploration following the low dose of apomorphine was not antagonised by remoxipride pretreatment. The results demonstrated that remoxipride has an interesting and unique profile of dopamine antagonistic effects in rat behavioural models.
Psychopharmacology, 1991
The effect of the selective D1 antagonist, SCH 23390, and the selective D2 antagonist, spiperone, was investigated in rats trained to self-administer intravenous cocaine on a fixed-ratio (FR) 5 schedule of reinforcement. Both SCH 23390 and spiperone pretreatment increased responding up to doses of 10.0 gg/kg, and decreased responding at higher doses. Since rate of responding maintained by a drug can be influenced by factors other than its reinforcing efficacy, behavior maintained by cocaine was also investigated under a progressive-ratio schedule. The breaking point obtained under this schedule is used as a measure of the efficacy of the reinforcer and this value is not exclusively determined by response rate. With the progressive-ratio schedule, both SCH 23390 and spiperone produced dose-dependent decreases in the highest ratio completed in rats self-administering cocaine. The results obtained using the FR 5 and progressive-ratio schedules suggest that both D1 and D2 receptors are involved in mediating the reinforcing effects of cocaine.