Evidence that a preferred substrate for type b monoamine oxidase mediates stimulus properties of MAO inhibitors: A possible role for β-phenylethylamine in the cocaine cue

Colpaert, Françis C.; Niemegeers, C. J. E.; Janßen, Paul

doi:10.1016/0091-3057(80)90273-7

Cited by 35 publications

(10 citation statements)

References 25 publications

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“…Selegiline was the only compound that fully substituted. These findings are in contrast to an earlier study in which a number of MAO-B or non-selective MAO inhibitors fully substituted for the discriminative stimulus effects of 5 mg/kg cocaine (Colpaert et al, 1980), including two that only produced partial substitution in the present study (tranylcypromine and pargyline). In that study, only clorgyline, a MAO-A selective inhibitor failed to fully substitute.…”

Section: Short-term Effectscontrasting

confidence: 56%

“…Selegiline has also fully substituted for the discriminative stimulus effects of cocaine in rats (Colpaert et al 1980;Yasar et al 1994) and pigeons (Johanson and Barrett, 1993). These findings raise the question of why selegiline was more efficacious at producing cocaine-like subjective effects than other MAO inhibitors.…”

Section: Short-term Effectsmentioning

confidence: 99%

“…Selegiline (17 mg/kg) fully substituted in rats trained to discriminate 10 mg/kg cocaine from saline (Yasar et al, 1994). A number of other MAO inhibitors fully substituted for the discriminative stimulus effects of 5 mg/kg cocaine, including pargyline [MAO-B selective, (Edwards and Pak, 1979)], and tranylcypromine, nialamide, pheniprazine (nonselective, Neff and Yang, 1974), whereas clorgyline [MAO-A selective (Salach et al, 1979)] failed to fully substitute (Colpaert et al, 1980). In addition, selegiline produced small increases in the effects of low doses of cocaine (Yasar et al, 1994).…”

mentioning

confidence: 99%

“…The immediate effects of the MAO inhibitors appear to be psychostimulant-like, as they substitute for the discriminative stimulus effects of cocaine (Colpaert et al, 1980;Johanson and Barrett, 1993;Yasar et al, 1994), and of amphetamine (Porsolt et al, 1984;Yasar et al, 1993). Selegiline (17 mg/kg) fully substituted in rats trained to discriminate 10 mg/kg cocaine from saline (Yasar et al, 1994).…”

mentioning

confidence: 99%

“…A second purpose was to assess the role of MAO-subtype selectivity, as one earlier study had suggested that only MAO-B inhibitors substituted for cocaine (Colpaert et al, 1980). To this end, the effects of the nonselective MAO inhibitors tranylcypromine and phenelzine (Neff and Yang, 1974), the MAO-A selective compound clorgyline (Salach et al, 1979), and the MAO-B selective compounds selegiline and pargyline (Edwards and Pak, 1979;Salach et al, 1979) were selected for testing.…”

mentioning

confidence: 99%

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Effects of monoamine oxidase inhibitors on cocaine discrimination in rats

Gatch

Taylor

Flores

et al. 2006

Behavioural Pharmacology

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This study tested the time course of the discriminative stimulus effects of inhibitors of monoamine oxidase (MAO) alone or in combination with cocaine. Male Sprague-Dawley rats were trained to discriminate cocaine (10 mg/kg, i.p.) from saline using a two-lever choice methodology. The nonselective MAO inhibitors tranylcypromine (0.01 to 5 mg/kg) and phenelzine (1 to 25 mg/kg), the MAO-A selective compound clorgyline (1 to 25 mg/kg), and the MAO-B selective compounds pargyline (0.005 to 50 mg/kg) and selegiline (1 to 25 mg/kg) were tested for substitution 15 min or 24 hr following administration, and in combination with 10 mg/kg of cocaine 24 and 48 hr after administration. At 15 min, selegiline fully substituted for the discriminative stimulus effects of cocaine, whereas all other compounds partially substituted. At 24 hr, substitution of cocaine was diminished for all compounds except phenelzine, which produced a greater amount of substitution at 24 hr than at 15 min. When cocaine was administered 24 hr following clorgyline, selegiline, pargyline, and phenelzine, cocaine-appropriate responding was attenuated at intermediate doses of these drugs, whereas the highest doses did not alter cocaine-lever responding. All compounds except selegiline substantially decreased response rate and produced various adverse effects. At 48 hr, the effects of all compounds except phenelzine were markedly reduced. Selectivity for MAO-A or B did not predict the ability to substitute for or attenuate the subjective effects of cocaine. These findings suggest that MAO inhibitors can modulate the discriminative stimulus effects of cocaine for at least 24 hr, and may be useful for treatment of cocaine abuse.

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Section: Short-term Effectscontrasting

confidence: 56%

Section: Short-term Effectsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of monoamine oxidase inhibitors on cocaine discrimination in rats

Gatch

Taylor

Flores

et al. 2006

Behavioural Pharmacology

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Effects of putative α‐adrenoceptor antagonists and of other compounds on the loss of the righting reflex and on exophthalmia induced by xylazine in the rat

Colpaert

1986

Drug Development Research

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Colpaert, F.C.: Effects of putative a-adrenoceptor antagonists and of other compounds on the loss of the righting reflex and on exophthalmia induced by xylazine in the rat. Drug Dev. Res. 7:125-140, 1986. lntraperitoneal injection of 20 mg/kg of xylazine causes loss of the righting reflex (LRR) and exophthalmia in the rat. The experiments determined some of the pharmacological characteristics of these responses to xylazine. The putative a2-adrenoceptor antagonists yohimbine, piperoxan, CGS 7525 A, and idazoxan blocked the LRR response; tolazoline, phentolamine, and salbutamol attenuated the response to some extent, whereas prazosin, aceperone, and phenoxybenzamine exerted no apparent effect. The putative a2-agonists clonidine, guanabenz, guanfacine, guanoxabenz, tiamenidine, and naphazoline were identified in an earlier study as acting only as partial agonists in depressing rat behavior and were found here to antagonize partially the LRR response. Other compounds that attenuated but did not block the response either have some affinity for and perhaps act as partial antagonists at a2-receptors (e.g., phentolamine, LSD, lisuride) or exert some arousing or behaviorally stimulating action (e.g., cocaine, nomifensine, tranylcypromine, apomorphine). Arousing sensory stimulation also produced a partial attenuation of the LRR response. The xylazine-induced exophthalmia appeared responsive to the putative alantagonists prazosin and aceperone, and other drugs exerting al-antagonist activity also antagonized the exophthalmia. The doses at which compounds antagonize xylazineReceived final version September 11, 1985; accepted September 12, 1985 Address reprint requests to Dr. F.C. Colpaert, Department of Psychopharmacology, Janssen Pharmaceutica, Turnhoutseweg 30, B-2340 Beerse, Belgium. 0 1986 Alan R. Liss, Inc. 126Colpaert induced LRR and exophthalmia in rat might offer an estimate of the compounds' in vivo potency in acting as antagonists at a2-and a,-adrenoceptors, respectively.

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Interactions of haloperidol with discriminative responding controlled by 10 mg/kg of cocaine in rats

Colpaert

1986

Drug Development Research

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Colpaert, F.C.:Interactions of haloperidol with discriminative responding controlled by 10 mg/kg of cocaine in rats. Drug Dev. Res. 9:125-131, 1986. Nine rats were trained to discriminate 10 mglkg of cocaine HCI from saline in a two-lever food-reinforced drug discrimination procedure. Saline and 0.31-10 mglkg doses of cocaine were tested for generalization after pretreatment with either vehicle or 0.04 and 0.16 mgl kg of haloperidol. The 0.04 and 0.16 mg/kg doses of haloperidol produced a 2.3 and 5.0-fold shift to the right, respectively, of the cocaine generalization gradient. Extrapolation of the generalization data suggests that about 3 mg/kg of haloperidol is required to antagonize completely the discriminative effects of the 10 mg/kg training dose of cocaine. Cocaine (0.63 mglkg) reversed the rate-depressant effects of 0.04 mglkg of haloperidol, but even 10 mglkg only partially attenuated the behavioral depression produced by 0.16 mglkg of haloperidol. Also, up to 10 mg/kg doses of cocaine exerted no reliable effect on the alternative lever responding produced by 0.04 or 0.16 mg/kg of haloperidol. The data suggest that a 2.3-5.0-fold shift of the cocaine gradient, but not a complete blockade of the discriminative effects of the 10 mglkg training dose of cocaine, can be achieved with doses of haloperidol at which the drug presumably interacts in a specific manner with dopamine receptors in the brain.

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Evidence that a preferred substrate for type b monoamine oxidase mediates stimulus properties of MAO inhibitors: A possible role for β-phenylethylamine in the cocaine cue

Cited by 35 publications

References 25 publications

Effects of monoamine oxidase inhibitors on cocaine discrimination in rats

Effects of monoamine oxidase inhibitors on cocaine discrimination in rats

Effects of putative α‐adrenoceptor antagonists and of other compounds on the loss of the righting reflex and on exophthalmia induced by xylazine in the rat

Interactions of haloperidol with discriminative responding controlled by 10 mg/kg of cocaine in rats

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