Subcutaneous injection of an analog of neuropeptide FF precipitates morphine abstinence syndrome

Malin, David H.; Lake, John R.; Arcangeli, K'Anne R.; Deshotel, Karen D.; Hausam, David D.; Witherspoon, Wendi E.; Carter, Victoria A.; Yang, Hongdian; Pal, Biman; Burgess, Kevin

doi:10.1016/0024-3205(93)90601-x

Cited by 26 publications

(6 citation statements)

References 16 publications

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“…The NPFFR1-selective systemically active agonists RFamide and dansyl-PQRFamide precipitated morphine abstinence syndrome [23,24], while the NPFFR1-selective systemically active antagonist dansyl-PQRamide attenuated morphine tolerance, restoring the analgesic effect of morphine [10]. Thus AC-263093 reversal of morphine tolerance coupled with its functional inhibition of NPFFR1 is consistent with the hypothesis that the NPFFR1 stimulation has anti-opiate effects in subjects that have been exposed to chronic opiate administration, while NPFFR1 inhibition may alleviate some effects of such opiate exposure.…”

Section: Discussionmentioning

confidence: 99%

Reversal of morphine tolerance by a compound with NPFF receptor subtype-selective actions

Malin

Henceroth

Izygon

et al. 2015

Neuroscience Letters

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Neuropeptide FF (NPFF) modulates opiate actions. It has pro-nociceptive effects, primarily through the NPFF receptor 1 subtype, and anti-nociceptive effects, primarily through the NPFFR2 subtype. AC-263093 is a small l, organic, systemically active molecule that was previously shown to functionally activate NPFFR2, but not NPFFR1. It was hypothesized that AC-263093 would attenuate morphine tolerance. Rats were tested for radiant heat tail-flick latency before and after 5 mg/kg morphine sulfate s.c. They were then rendered morphine-tolerant by continuous subcutaneous infusion of 17.52 mg/kg/day morphine sulfate. On the seventh day of infusion, they were retested for analgesia 10 and 20 min after 5mg/kg morphine sulfate s.c. Tolerance was indicated by reduction of morphine analgesia from the pre-infusion test. Fifty minutes prior to morphine challenge, rats received either 10 mg/kg i.p. AC-263093 or injection vehicle alone. AC-2623093-treated rats had far smaller tolerance scores than control rats. This drug effect was significant, p = 0.015. The same dose of AC-263093 had almost no analgesic effect in non-tolerant, saline-infused rats. In vitro experiments revealed that AC-263093 had equal affinity for NPFFR1 and NPFFR2, and functionally inactivated NPFFR1, in addition to its previously shown ability to activate NPFFR2. Thus, altering the balance between activation of NPFF receptor subtypes may provide one approach to reversing opiate tolerance.

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Section: Discussionmentioning

confidence: 99%

Reversal of morphine tolerance by a compound with NPFF receptor subtype-selective actions

Malin

Henceroth

Izygon

et al. 2015

Neuroscience Letters

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“…The nonopioid peptide, neuropeptide FF (NPFF), has potent antiopiate actions and may play a role in opiate dependence (Malin et al 1990). Systemic injection of a systemically active NPFF analog precipitated a withdrawal syndrome in morphine-dependent rats (Malin et al 1993b) and also in nicotine-dependent rats (Malin et al 1996b). There are opposing interactions between kappa-opiate receptors and other opiate receptors.…”

Section: Endogenous Opiate Mechanismsmentioning

confidence: 98%

Rodent Models of Nicotine Withdrawal Syndrome

Malin

Goyarzu

2009

Handbook of Experimental Pharmacology

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Simple, rapid and inexpensive rodent models of nicotine physical dependence and withdrawal syndrome have proved useful for preliminary screening of smoking cessation treatments. They have led to an exponential increase of knowledge regarding the underlying neurobiological mechanisms of dependence and withdrawal syndrome. The human nicotine withdrawal syndrome in smoking cessation is variable and multidimensional, involving irritability, anxiety, depression, cognitive and attentional impairments, weight gain, sleep disturbances, and craving for nicotine. Aside from sleep disturbances, analogous phenomena have been seen in rodent models using different measures of withdrawal intensity. It appears likely that different withdrawal phenomena may involve some partially divergent mechanisms. For example, depression-like phenomena may involve alterations in mechanisms such as the mesolimbic dopamine pathway from the ventral tegmental area to the nucleus accumbens. Irritability and anxiety may involve alterations in endogenous opioid systems and other regions, such as the amygdala. This chapter reviews many additional anatomical, neurochemical, and developmental elements that impact nicotine physical dependence.

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“…Finally, nicotine abstinence syndrome was precipitated by injection of a systemically active analog of neuropeptide FF (Malin et al 1996b). Neuropeptide FF (NPFF) has antiopiate e¤ects and has been shown to contribute to opiate tolerance and dependence (Malin et al 1990a(Malin et al ,b, 1993a(Malin et al , 1995Lake et al 1991).…”

Section: Introductionmentioning

confidence: 99%

The nitric oxide synthesis inhibitor nitro- L -arginine ( L -NNA) attenuates nicotine abstinence syndrome in the rat

Malin¹,

Lake²,

Shenoi³

et al. 1998

Psychopharmacology

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Nitric oxide synthesis contributes to opiate tolerance and dependence. Nicotine dependence and abstinence syndrome in the rat appear to involve opiate mechanisms. Therefore, it was postulated that nitric oxide synthase (NOS) activity might be essential for the expression of nicotine abstinence syndrome. Twenty-one rats were rendered dependent by SC infusion of 9 mg/kg per day nicotine tartrate via Alzet osmotic minipump. Rats were pretreated SC with vehicle alone, or with 18 or 30 mg/kg of the NOS inhibitor L-NNA (nitro-L-arginine). Thirty minutes later, rats were challenged by 1 mg/kg of the nicotinic antagonist mecamylamine SC and observed for 30 additional minutes. Rats pretreated with vehicle displayed a total of 68.7+/-8.0 mecamylamine-precipitated abstinence signs (mean+/-SEM), while those receiving 18 or 30 mg/kg L-NNA had 12.7+/-2.0 and 5.1+/-1.7 signs, respectively. All three groups differed significantly from one another according to Dunn's post-hoc procedure. Rats pretreated with L-NNA combined with an excess of the NOS substrate L-arginine had significantly more mecamylamine-precipitated abstinence signs than rats receiving L-NNA combined with D-arginine. Also, D-NNA, which does not selectively bind to NOS, was significantly less effective than L-NNA in preventing mecamylamine-precipitated abstinence syndrome. Additional studies determined the effect of L-NNA on spontaneous nicotine abstinence syndrome. Rats were assessed for abstinence signs at 17 and 20 h after termination of nicotine infusion. They received injections of 9, 18, or 30 mg/kg L-NNA SC or vehicle alone immediately before the 20-h observation; all rats were observed for 30 min. Signs at 20 h (post-injection) as a percentage of signs at 17 h (pre-injection) declined significantly as a function of L-NNA dose. Once again, this effect was attenuated significantly more by co-administration of L-arginine than by D-arginine. The overall pattern of results suggests that nitric oxide synthesis is critical to the expression of nicotine abstinence syndrome.

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Subcutaneous injection of an analog of neuropeptide FF precipitates morphine abstinence syndrome

Cited by 26 publications

References 16 publications

Reversal of morphine tolerance by a compound with NPFF receptor subtype-selective actions

Reversal of morphine tolerance by a compound with NPFF receptor subtype-selective actions

Rodent Models of Nicotine Withdrawal Syndrome

The nitric oxide synthesis inhibitor nitro- L -arginine ( L -NNA) attenuates nicotine abstinence syndrome in the rat

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