The δ-Opioid Receptor Agonist SNC80 [(+)-4-[α(R)-α-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-(3-methoxybenzyl)-N,N-diethylbenzamide] Synergistically Enhances the Locomotor-Activating Effects of Some Psychomotor Stimulants, but Not Direct Dopamine Agonists, in Rats

Jutkiewicz, Emily M.; Baladi, Michelle G.; Folk, J.E.; Rice, Kenner C.; Woods, James H.

doi:10.1124/jpet.107.123844

Cited by 15 publications

(20 citation statements)

References 28 publications

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“…NTI administered in vivo completely blocked the SNC80 enhancement of dopamine overflow elicited by 100 µM amphetamine sulfate in vitro (F(33,231) = 5.14, p < 0.01). This same treatment paradigm with NTI attenuated the ability of SNC80 to enhance amphetaminemediated locomotor stimulation in rats (Jutkiewicz et al, 2008). This finding establishes that delta opioid receptor activation is necessary for SNC80 to enhance amphetamine-mediated dopamine efflux.…”

Section: Effect Of the Delta Selective Antagonist Naltrindole (Nti)supporting

confidence: 54%

“…Although a 3 h pretreatment with SNC80 also produced the greatest enhancement of amphetamine-mediated behaviors in vivo (Jutkiewicz et al, 2008), this long time course does not correspond with the more rapid onset of behavioral effects seen with administration of SNC80 alone. For example, SNC80 induces locomotor activity immediately after systemic administration Jutkiewicz et al, 2008).…”

Section: Effect Of In Vivo Snc80 On Amphetamine-mediated Dopamine Effmentioning

confidence: 92%

“…For example, SNC80 induces locomotor activity immediately after systemic administration Jutkiewicz et al, 2008). This may suggest the effect of SNC80 on amphetamine-mediated dopamine efflux is due to induction of a persistent change rather than a direct acute action of SNC80.…”

Section: Effect Of In Vivo Snc80 On Amphetamine-mediated Dopamine Effmentioning

confidence: 99%

“…SNC80 produced a marked increase in amphetamine-mediated behaviors, peaking 3 h after administration (Jutkiewicz et al, 2008). Striatal preparations from rats treated 3 h previously with SNC80 (10 mg/kg, s.c.) were evaluated for the amount of dopamine released in response to different concentrations of amphetamine sulfate.…”

Section: Effect Of In Vivo Snc80 On Amphetamine-mediated Dopamine Effmentioning

confidence: 99%

“…For example, DPDPE increased cocaine-induced locomotor activity in rats (Waddell and Holtzman, 1998) and SNC80, in combination with cocaine, resulted in leftward shifts in the discriminative stimulus effects of cocaine in primates (Negus et al, 1998;Rowlett and Spealman, 1998). SNC80 has also been shown to enhance the locomotor stimulating effects of amphetamines and other psychomotor stimulants which act at the dopamine transporter (Mori et al, 2006;Jutkiewicz et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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The selective delta opioid agonist SNC80 enhances amphetamine-mediated efflux of dopamine from rat striatum

et al. 2008

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The highly selective delta opioid agonist, SNC80, elicits dopamine-related behaviors including locomotor stimulation and conditioned place-preference. In contrast, it has been reported that SNC80 fails to promote dopamine efflux from the striatum of freely moving rats. However, SNC80 does enhance behavioral responses to the stimulants, amphetamine and cocaine, suggesting an interaction between delta opioids and psychostimulants. Since the increase in locomotor activity elicited by amphetamine and related stimulants acting at the dopamine transporter is associated with increases in extracellular concentrations of dopamine within the striatum, we hypothesized that SNC80 enhances this activity by potentiating the overflow of dopamine through the transporter. To test this hypothesis, striatal preparations from Sprague-Dawley rats were assayed for dopamine efflux in response to amphetamine challenge. SNC80 was given either in vivo or in vitro directly to rat striatal tissue, prior to in vitro amphetamine challenge. Both in vivo and in vitro administration of SNC80 enhanced amphetamine-mediated dopamine efflux in a concentration-and time-dependent manner. However, SNC80 in either treatment paradigm produced no stimulation of dopamine efflux in the absence of amphetamine. The effect of SNC80 on amphetamine-mediated dopamine overflow, but not the effect of amphetamine alone, was blocked by the delta selective antagonist, naltrindole and was also observed with other delta agonists. The results of this study demonstrate that even though SNC80 does not stimulate dopamine efflux alone, it is able to augment amphetamine-mediated dopamine efflux through a delta opioid receptor mediated action locally in the striatum.

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Section: Effect Of the Delta Selective Antagonist Naltrindole (Nti)supporting

confidence: 54%

Section: Effect Of In Vivo Snc80 On Amphetamine-mediated Dopamine Effmentioning

confidence: 92%

Section: Effect Of In Vivo Snc80 On Amphetamine-mediated Dopamine Effmentioning

confidence: 99%

Section: Effect Of In Vivo Snc80 On Amphetamine-mediated Dopamine Effmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The selective delta opioid agonist SNC80 enhances amphetamine-mediated efflux of dopamine from rat striatum

et al. 2008

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The Role of δ-Opioid Receptors in Brain Ionic Homeostasis Under Physiological Condition

Chao¹,

Xia²

2015

Neural Functions of the Delta-Opioid Receptor

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Effects of the delta-opioid agonist SNC80 on the abuse liability of methadone in rhesus monkeys: a behavioral economic analysis

et al. 2011

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Rationale Delta-opioid agonists enhance the antinociceptive efficacy of methadone and other mu-opioid agonists. However, relatively little is known about the degree to which delta agonists might enhance the abuse-related effects of mu agonists. Objective This study used a behavioral economic approach to examine effects of the delta agonist SNC80 [(+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxy-benzyl]-N,N-diethylbenzamide] on the reinforcing effects of methadone in a drug self-administration assay. Interactions between SNC80 and cocaine were also examined for comparison. Methods Rhesus monkeys (n=4), surgically implanted with indwelling intravenous catheters, were tested in two phases. In phase 1, drug self-administration dose-effect curves for methadone (0.0032–0.1 mg/kg/injection (inj)) and cocaine (0.0032–0.32 mg/kg/inj) alone were determined under a fixed-ratio 10 (FR 10) schedule of reinforcement. In phase 2, FR values were increased every 3 days (FR 1–FR 1800) during availability of methadone alone (0.032 mg/kg/inj) and in combination with varying proportions of SNC80 (0.1:1, 0.3:1, and 0.9:1 SNC80/methadone) or of cocaine alone (0.032 mg/kg/inj) and in combination with varying proportions of SNC80 (0.33:1, 1:1, and 3:1 SNC80/ cocaine). Demand curves related drug intake to FR price, and measures of reinforcement were derived. Results Methadone and cocaine alone each functioned as a reinforcer. SNC80 did not alter measures of reinforcement for either methadone or cocaine. Conclusions SNC80 at proportions previously shown to enhance methadone-induced antinociception did not enhance the abuse-related effects of methadone. These results support the proposition that delta agonists may selectively enhance mu agonist analgesic effects without enhancing mu agonist abuse liability.

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The δ-Opioid Receptor Agonist SNC80 [(+)-4-[α(R)-α-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-(3-methoxybenzyl)-N,N-diethylbenzamide] Synergistically Enhances the Locomotor-Activating Effects of Some Psychomotor Stimulants, but Not Direct Dopamine Agonists, in Rats

Cited by 15 publications

References 28 publications

The selective delta opioid agonist SNC80 enhances amphetamine-mediated efflux of dopamine from rat striatum

The selective delta opioid agonist SNC80 enhances amphetamine-mediated efflux of dopamine from rat striatum

The Role of δ-Opioid Receptors in Brain Ionic Homeostasis Under Physiological Condition

Effects of the delta-opioid agonist SNC80 on the abuse liability of methadone in rhesus monkeys: a behavioral economic analysis

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