β2-Subunit-containing nicotinic acetylcholine receptors are involved in nicotine-induced increases in conditioned reinforcement but not progressive ratio responding for food in C57BL/6 mice

Brunzell, Darlene H.; Chang, Jessica R.; Schneider, Brandon; Olausson, Peter; Taylor, Jane R.; Picciotto, Marina R.

doi:10.1007/s00213-005-0099-z

Cited by 68 publications

(63 citation statements)

References 63 publications

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“…DHβE, an α4β2-selective antagonist, effectively decreased the nicotine-enhanced lever responses. This finding is in line with previous studies showing that knockout of β2-subunit of the nAChRs cancelled the ability of nicotine to enhance responding for a food-conditioned reinforcement (Brunzell et al 2006) and that DHβE reversed nicotine-induced potentiation of the electrical stimulation reward (Harrison et al 2002;Kenny and Markou 2006). However, the α7-selective antagonist MLA did not change magnitude of nicotine-enhanced responding.…”

Section: Discussionsupporting

confidence: 92%

Reinforcement enhancing effect of nicotine and its attenuation by nicotinic antagonists in rats

et al. 2007

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Rationale-Recent studies have demonstrated that nicotine can enhance operant responding for other nonpharmacological reinforcing stimuli. However, the nature of the reinforcement-enhancing effect of nicotine remains largely unknown.Objective-The present study determined the dose dependency of the ability of nicotine to increase lever-pressing responses maintained by a compound visual stimulus (VS) in rats and examined its sensitivity to pharmacological antagonism of nicotinic acetylcholine receptors (nAChRs). Materials and methods-MaleSprague-Dawley rats were trained in daily 1-h sessions to lever press for delivery of a VS (1 s lever light on and 60 s house light off) on a fixed ratio 5 schedule. During these sessions, eight scheduled response-independent intravenous infusions of nicotine (total amount: 0, 0.06, 0.12, 0.24, 0.48 mg kg −1 h −1 ) were delivered. In pharmacological tests, a nonselective nAChR antagonist mecamylamine, α4β2-selective antagonist dihydro-β-erythroidine (DHβE), and α7-selective antagonist methyllycaconitine (MLA) were administered in different groups of rats 30 min before the session.Results-The VS maintained a moderate level of lever-pressing responses and nicotine dosedependently increased responses for the VS presentations. Preteatment of mecamylamine and DHβE but not MLA significantly attenuated the nicotine-enhanced responding. However, mecamylamine had no effect on responding for the VS in rats that received scheduled saline infusions.Conclusions-These results demonstrate dose dependency of the reinforcement-enhancing effect of nicotine and suggest that activation of the α4β2-but not α7-containing nAChRs may mediate this effect.

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Section: Discussionsupporting

confidence: 92%

Reinforcement enhancing effect of nicotine and its attenuation by nicotinic antagonists in rats

et al. 2007

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“…The possibility that our manipulations also affect instrumental learning processes can, however, not be completely excluded. In support of our conclusions, the increase in instrumental performance observed after previous oral cocaine exposure (Miles et al, 2004) has been argued to involve motivational alterations consistent with the ability of chronic nicotine treatment to increase progressive ratio responding in mice (Brunzell et al, 2006). Furthermore, dopamine transporter knock-out mice, in which extracellular dopamine levels are increased, display both enhanced ⌬FosB immunoreactivity and food-reinforced motivation, but not altered learning (Cagniard et al, 2006).…”

Section: Discussionsupporting

confidence: 85%

ΔFosB in the Nucleus Accumbens Regulates Food-Reinforced Instrumental Behavior and Motivation

Olausson¹,

Jentsch²,

Tronson³

et al. 2006

J. Neurosci.

102

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Alterations in motivation have been implicated in the pathophysiology of several psychiatric disorders, including substance abuse and depression. Repeated exposure to drugs of abuse or stress is known to persistently induce the transcription factor ⌬FosB in the nucleus accumbens (NAc) and dorsal striatum, effects hypothesized to contribute to neuroadaptations in dopamine-regulated signaling. Little is known, however, about the specific involvement of ⌬FosB in dysregulation of appetitively motivated behaviors. We show here that inducible overexpression of ⌬FosB in NAc and dorsal striatum of bitransgenic mice, or specifically in the NAc core of rats by use of viralmediated gene transfer, enhanced food-reinforced instrumental performance and progressive ratio responding. Very similar behavioral effects were found after previous repeated exposure to cocaine, amphetamine, MDMA [(ϩ)-3,4-methylenedioxymethamphetamine], or nicotine in rats. These results reveal the powerful regulation of motivational processes by ⌬FosB, and provide evidence that drug-induced alterations in gene expression via induction of ⌬FosB within the NAc core may play a critical role in the impact of motivational influences on instrumental behavior.

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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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β2-Subunit-containing nicotinic acetylcholine receptors are involved in nicotine-induced increases in conditioned reinforcement but not progressive ratio responding for food in C57BL/6 mice

Abstract: These data show that nicotine exposure enhances conditioned reinforcement in mice and indicate that beta2*nAChRs are necessary for nicotine-dependent enhancement of incentive aspects of motivation but not motivation for primary reinforcement measured by progressive ratio responding.

Cited by 68 publications

References 63 publications

Reinforcement enhancing effect of nicotine and its attenuation by nicotinic antagonists in rats

Reinforcement enhancing effect of nicotine and its attenuation by nicotinic antagonists in rats

ΔFosB in the Nucleus Accumbens Regulates Food-Reinforced Instrumental Behavior and Motivation

Galanin Protects Against Behavioral and Neurochemical Correlates of Opiate Reward

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