Modulation of the Discriminative Stimulus Effects of d-Amphetamine by Mu and Kappa Opioids in Squirrel Monkeys

Powell, Kelly R.; Holtzman, Stephen G.

doi:10.1016/s0091-3057(99)00183-5

Cited by 19 publications

(11 citation statements)

References 22 publications

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“…However, previous reports indicate potent blockade of the d-amphetamine discriminative cue by these antagonists (Callahan et al, 1991; Exner et al, 1989; Powell and Holtzman, 2000; West et al, 1995). Considered together with previous findings, the current results strongly indicate MDPV and MEPH stimulus generalization for d-amphetamine can be attributed to their actions on dopamine receptors.…”

Section: Discussionmentioning

confidence: 73%

Effects of D1 and D2 receptor antagonists on the discriminative stimulus effects of methylendioxypyrovalerone and mephedrone in male Sprague-Dawley rats trained to discriminate d-amphetamine

Harvey

Burroughs

Baker

2017

Behavioural Pharmacology

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Psychopharmacology research has amassed substantial evidence for similarities between synthetic cathinones and other commonly abused psychostimulants. Few studies have utilized drug discrimination methods to investigate synthetic cathinones, and the precise neurochemical substrates underlying their interoceptive effects have not been examined. The present study assessed the involvement of D1 and D2 dopaminergic receptors in the stimulus effects of MDPV and mephedrone in rats trained to discriminate d-amphetamine. Eight male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg d-amphetamine (AMPH) from saline. Dose-response curves were then generated with AMPH (0.0 – 1.0 mg/kg), MDPV (0.0 – 1.0 mg/kg), and mephedrone (MEPH) (0.0 – 2.0 mg/kg). Subsequently, Sch 39166 (0.3 mg/kg) and haloperidol (0.5 mg/kg) were administered in combination with select doses of MDPV and MEPH. Both MDPV and MEPH produced full substitution for AMPH. Sch 39166 produced a downward shift in the MDPV and MEPH dose response curves and haloperidol produced similar results with MDPV. These preliminary findings indicate MDPV and MEPH produce interoceptive stimuli that are similar to those produced by d-amphetamine and that D1 and D2 dopamine receptors contribute to these effects. Additional studies are warranted to investigate the contribution of other receptor mechanisms involved in the interoceptive stimuli produced by synthetic cathinones.

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Section: Discussionmentioning

confidence: 73%

Effects of D1 and D2 receptor antagonists on the discriminative stimulus effects of methylendioxypyrovalerone and mephedrone in male Sprague-Dawley rats trained to discriminate d-amphetamine

Harvey

Burroughs

Baker

2017

Behavioural Pharmacology

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“…Although our results do not support a role for the SERT in modulating the shared DS effects of heroin and cocaine, these findings do not rule out the possibility of a role of specific 5-HT receptor subtypes. For example, the selective 5-HT 1A agonist 8-OH-DPAT (8-hydroxy-2-dipropylaminotetralin) attenuated the DS effects of morphine in morphinetrained rats (Powell et al, 1994), suggesting an inhibitory influence of 5-HT 1A receptor stimulation on the interoceptive effects of morphine. Although 5-HT 1A receptor stimulation likely occurs indirectly via blockade of the SERT, the possibility of involvement of specific 5-HT receptor subtypes deserves additional evaluation.…”

Section: Discussionmentioning

confidence: 99%

Cocaine-Like Discriminative Stimulus Effects of Heroin: Modulation by Selective Monoamine Transport Inhibitors

Rowlett¹

2004

J Pharmacol Exp Ther

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In previous studies, heroin was shown to engender cocaine-like discriminative stimulus (DS) effects; however, the mechanisms underlying the cocaine-like effects of heroin are unknown. The present study evaluated the extent to which the shared DS effects of heroin and cocaine involve common monoaminergic mechanisms of action. In squirrel monkeys discriminating cocaine (0.3 mg/kg) from saline, heroin engendered full or partial substitution for cocaine in three of four monkeys. Pretreatment with the selective dopamine transport inhibitor 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine (GBR 12909) dose dependently enhanced the cocaine-like DS effects of heroin in these three monkeys as well as the DS effects of cocaine in all subjects. Neither talsupram, a noradrenergic transport inhibitor, nor prazosin, a noradrenergic antagonist selective for ␣-1 receptors, systematically altered the cocainelike DS effects of heroin at doses that enhanced (talsupram) or attenuated (prazosin) the DS effects of cocaine. Pretreatment with the serotonin uptake inhibitor citalopram similarly failed to alter the cocaine-like DS effects of heroin at doses that attenuated the DS effects of cocaine. Altogether, these findings suggest that heroin shares DS effects with cocaine in a subset of monkeys, and these cocaine-like effects are mediated at least in part by enhanced dopaminergic activity. Unlike the DS effects of cocaine itself, however, the cocaine-like DS effects of heroin do not appear to involve either noradrenergic or serotonergic mechanisms.

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“…In addition, U69,593 attenuates the psychomotor stimulant effects of amphetamine and cocaine and modulates neurotoxic effects of methamphetamine [341–343]. Furthermore, U69,593 attenuates the discriminative stimulus effects of amphetamine in squirrel monkeys [344], albeit with large inter-individual differences.…”

Section: Opioid-based Medication Discoverymentioning

confidence: 99%

Hypothesis-Driven Medication Discovery for the Treatment of Psychostimulant Addiction

Xi¹,

Gardner²

2008

CDAR

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Psychostimulant abuse is a serious social and health problem, for which no effective treatments currently exist. A number of review articles have described predominantly ‘clinic’-based pharmacotherapies for the treatment of psychostimulant addiction, but none have yet been shown to be definitively effective for use in humans. In the present article, we review various ‘hypothesis’- or ‘mechanism’-based pharmacological agents that have been studied at the preclinical level and evaluate their potential use in the treatment of psychostimulant addiction in humans. These compounds target brain neurotransmitter or neuromodulator systems, including dopamine (DA), γ-aminobutyric acid (GABA), endocannabinoid, glutamate, opioid and serotonin, which have been shown to be critically involved in drug reward and addiction. For drugs in each category, we first briefly review the role of each neurotransmitter system in psychostimulant actions, and then discuss the mechanistic rationale for each drug’s potential anti-addiction efficacy, major findings with each drug in animal models of psychostimulant addiction, abuse liability and potential problems, and future research directions. We conclude that hypothesis-based medication development strategies could significantly promote medication discovery for the effective treatment of psychostimulant addiction.

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Modulation of the Discriminative Stimulus Effects of d-Amphetamine by Mu and Kappa Opioids in Squirrel Monkeys

Cited by 19 publications

References 22 publications

Effects of D1 and D2 receptor antagonists on the discriminative stimulus effects of methylendioxypyrovalerone and mephedrone in male Sprague-Dawley rats trained to discriminate d-amphetamine

Effects of D1 and D2 receptor antagonists on the discriminative stimulus effects of methylendioxypyrovalerone and mephedrone in male Sprague-Dawley rats trained to discriminate d-amphetamine

Cocaine-Like Discriminative Stimulus Effects of Heroin: Modulation by Selective Monoamine Transport Inhibitors

Hypothesis-Driven Medication Discovery for the Treatment of Psychostimulant Addiction

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