Behavioral effects of morphine and cocaine in M1 muscarinic acetylcholine receptor-deficient mice

Carrigan, Kelly A.; Dykstra, Linda

doi:10.1007/s00213-006-0671-1

Cited by 31 publications

(24 citation statements)

References 40 publications

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“…Whereas mRNA levels for galanin receptors are low in the NAc, galanin receptor binding is quite prominent (Burgevin et al, 1995;Gustafson et al, 1996;Hawes and Picciotto, 2004;Kolakowski et al, 1998;Waters and Krause, 2000), indicating that localization of galanin receptors on DA terminals might regulate DA release. Galanin is also known to be a potent inhibitory modulator of basal acetylcholine (ACh) release in the striatum (Antoniou et al, 1997) and it has been demonstrated that M1-muscarinic receptors and high-affinity nicotinic receptors regulate the secondary rewarding effects of cues paired with a primary reinforcer such as morphine (Brunzell et al, 2006;Carrigan and Dykstra, 2007). Lack of galanin may therefore increase availability of ACh, thus increasing the sensitivity of GKO mice to opiates.…”

Section: Discussionmentioning

confidence: 99%

Galanin Protects Against Behavioral and Neurochemical Correlates of Opiate Reward

Hawes

Brunzell

Narasimhaiah

et al. 2007

Neuropsychopharmacol

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The mechanisms underlying responses to drugs of abuse have been widely investigated; however, less is known about pathways normally protective against the development of drug reinforcement. These pathways are also important since they may regulate individual differences in vulnerability to addiction. The neuropeptide galanin and its binding sites are expressed in brain areas important for drug reward. Previous studies have shown that centrally infused galanin attenuates morphine place preference and peripheral injection of galnon, a galanin agonist, decreases opiate withdrawal signs. The current studies in galanin knockout (GKO) mice examined the hypothesis that galanin is an endogenous negative regulator of opiate reward and identified downstream signaling pathways regulated by galanin. We show that GKO mice demonstrate increased locomotor activation following morphine administration, which is inhibited by acute administration of galnon. GKO mice also show enhanced morphine place preference, supporting the idea that galanin normally antagonizes opiate reward. In addition, morphine-induced ERK1/2 phosphorylation was increased in the VTA of both wild-type and GKO mice, but only the GKO mice showed increases in ERK1/2 and CREB phosphorylation in the amygdala or nucleus accumbens. Furthermore, a single systemic injection of galnon in GKO mice was sufficient to reverse some of the biochemical changes brought about by morphine administration. These data suggest that galanin normally attenuates behavioral and neurochemical effects of opiates; thus, galanin agonists may represent a new class of therapeutic targets for opiate addiction.

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Section: Discussionmentioning

confidence: 99%

Galanin Protects Against Behavioral and Neurochemical Correlates of Opiate Reward

Hawes

Brunzell

Narasimhaiah

et al. 2007

Neuropsychopharmacol

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“…Morphine- and cocaine- induced conditioned-place preference are attenuated by either genetic disruption of the M 1 muscarinic receptor or combining drug treatments with an antagonist for the M 1 receptor [144]. In these studies, knock-out or antagonist treated animals correspond to State A in Figure 1, with wild-type and vehicle treated animals corresponding to State B in which activation of the M 1 receptor allows ACh to facilitate food- or drug- reinforced behaviors.…”

Section: A Threshold Model For Cholinergic Effects On Reinforced Behamentioning

confidence: 99%

A threshold model for opposing actions of acetylcholine on reward behavior: Molecular mechanisms and implications for treatment of substance abuse disorders

Grasing

2016

Behavioural Brain Research

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The cholinergic system plays important roles in both learning and addiction. Medications that modify cholinergic tone can have pronounced effects on behaviors reinforced by natural and drug reinforcers. Importantly, enhancing the action of acetylcholine (ACh) in the nucleus accumbens and ventral tegmental area (VTA) dopamine system can either augment or diminish these behaviors. A threshold model is presented that can explain these seemingly contradictory results. Relatively low levels of ACh rise above a lower threshold, facilitating behaviors supported by drugs or natural reinforcers. Further increases in cholinergic tone that rise above a second upper threshold oppose the same behaviors. Accordingly, cholinesterase inhibitors, or agonists for nicotinic or muscarinic receptors, each have the potential to produce biphasic effects on reward behaviors. Pretreatment with either nicotinic or muscarinic antagonists can block drug- or food- reinforced behavior by maintaining cholinergic tone below its lower threshold. Potential threshold mediators include desensitization of nicotinic receptors and biphasic effects of ACh on the firing of medium spiny neurons. Nicotinic receptors with high- and low-affinity appear to play greater roles in reward enhancement and inhibition, respectively. Cholinergic inhibition of natural and drug rewards may serve as mediators of previously described opponent processes. Future studies should evaluate cholinergic agents across a broader range of doses, and include a variety of reinforced behaviors.

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“…These neuropharmacological properties have been associated with its weak stimulant effects in tests of locomotor activity and place preference (Li et al 2005). The antimuscarinic actions of AHN-1055 might be important, as muscarinic receptor stimulation is needed, at least in part, to generate drug-induced reward and reinforcement (Carrigan and Dykstra 2007;Crespo et al 2006). While neurochemical and behavioral evidence would support the potential use of this analog as a candidate treatment in cocaine addiction, neither its reinforcing nor its motivational properties, as measured in cost-benefit and relapse assays, have been previously investigated.…”

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confidence: 99%

A dopamine transport inhibitor with markedly low abuse liability suppresses cocaine self-administration in the rat

et al. 2009

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Registro de acceso restringido Este recurso no está disponible en acceso abierto por política de la editorial. No obstante, se puede acceder al texto completo desde la Universitat Jaume I o si el usuario cuenta con suscripción. Registre d'accés restringit Aquest recurs no està disponible en accés obert per política de l'editorial. No obstant això, es pot accedir al text complet des de la Universitat Jaume I o si l'usuari compta amb subscripció. Restricted access item This item isn't open access because of publisher's policy. The full--text version is only available from Jaume I University or if the user has a running suscription to the publisher's contents.

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Behavioral effects of morphine and cocaine in M1 muscarinic acetylcholine receptor-deficient mice

Abstract: These results suggest a modulatory role of the M1 muscarinic receptor in opioid antinociception and conditioned drug reward, and demonstrate the utility of M1 receptor knockout models for the determination of the role of the M1 subtype in the behavioral effects of morphine and cocaine.

Cited by 31 publications

References 40 publications

Galanin Protects Against Behavioral and Neurochemical Correlates of Opiate Reward

Galanin Protects Against Behavioral and Neurochemical Correlates of Opiate Reward

A threshold model for opposing actions of acetylcholine on reward behavior: Molecular mechanisms and implications for treatment of substance abuse disorders

A dopamine transport inhibitor with markedly low abuse liability suppresses cocaine self-administration in the rat

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