SSR591813, a Novel Selective and Partial  α<sub>4</sub>β<sub>2</sub> Nicotinic Receptor Agonist with  Potential as an Aid to Smoking Cessation

Cohen, Caroline; Bergis, Olivier; Galli, Frédéric; Lochead, Alister W.; Jegham, Samir; Biton, Bruno; Léonardon, Jacques; Avenet, Patrick; Sgard, Frédéric; Besnard, François; Graham, David Y.; Coste, Annick; Oblin, A.; Curet, O.; Voltz, C.; A, Gardes; Caille, D.; Perrault, Ghislaine; George, Pascal; Soubrié, Philippe; Scatton, B.

doi:10.1124/jpet.103.049262

Cited by 113 publications

(77 citation statements)

References 28 publications

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“…An important role of ␣4* nAChRs is also suggested by the evidence that activation of hypersensitive ␣4* nAChRs is sufficient to support nicotine place preference (Tapper et al, 2004). Yet, at the moment, the pharmacological evidence of the contribution of ␣4␤2* receptors to maintenance of nicotine self-administration is not conclusive, since the selectivity for ␣4␤2* with respect to ␣6␤2* nAChRs of available nicotinic antagonists or partial agonists (dihydro-␤-erythroidine, SSR591813 [(5aS,8S,10aR)-5a,6,9,10-tetrahydro,7H,11H-8,10a-methanopyrido[2Ј,3Ј:5,6]pyrano[2, 3-d] azepine], varenicline, UCI-30002 [N-(1,2,3,4-tetrahydro-1-naphthyl)-4-nitroaniline]) (Corrigall et al, 1994;Cohen et al, 2003;Rollema et al, 2007;Yoshimura et al, 2007) is not well established. We propose that both ␣6␤2 and ␣4␤2 receptors are necessary for (at least some of) the effects of nicotine on the DA system.…”

Section: Discussionmentioning

confidence: 99%

Nicotinic Acetylcholine Receptors in the Mesolimbic Pathway: Primary Role of Ventral Tegmental Area α6β2* Receptors in Mediating Systemic Nicotine Effects on Dopamine Release, Locomotion, and Reinforcement

Gotti¹,

Guiducci²,

Tedesco³

et al. 2010

J. Neurosci.

209

236

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␣6* nicotinic acetylcholine receptors (nAChRs) are highly and selectively expressed by mesostriatal dopamine (DA) neurons. These neurons are thought to mediate several behavioral effects of nicotine, including locomotion, habit learning, and reinforcement. Yet the functional role of ␣6* nAChRs in midbrain DA neurons is mostly unknown. The aim of this study was to determine the composition and in vivo functional role of ␣6* nAChR in mesolimbic DA neurons of male rats. Immunoprecipitation and immunopurification techniques coupled with cell-specific lesions showed that the composition of ␣6* nAChR in the mesostriatal system is heterogeneous, with (non-␣4)␣6␤2* being predominant in the mesolimbic pathway and ␣4␣6␤2* in the nigrostriatal pathway. We verified whether ␣6* receptors mediate the systemic effects of nicotine on the mesolimbic DA pathway by perfusing the selective antagonists ␣-conotoxin MII (CntxMII) (␣3/␣6␤2* selective) or ␣-conotoxin PIA (CntxPIA) (␣6␤2* selective) into ventral tegmental area (VTA). The intra-VTA perfusion of CntxMII or CntxPIA markedly decreased systemic nicotine-elicited DA release in the nucleus accumbens and habituated locomotion; the intra-VTA perfusion of CntxMII also decreased the rate of nicotine infusion in the maintenance phase of nicotine, but not of food, self-administration. Overall, the results of these experiments show that the ␣6␤2* nAChRs expressed in the VTA are necessary for the effects of systemic nicotine on DA neuron activity and DA-dependent behaviors such as locomotion and reinforcement, and suggest that ␣6␤2*-selective compounds capable of crossing the blood-brain barrier may affect the addictive properties of nicotine and therefore be useful in the treatment of tobacco dependence.

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Section: Discussionmentioning

confidence: 99%

Nicotinic Acetylcholine Receptors in the Mesolimbic Pathway: Primary Role of Ventral Tegmental Area α6β2* Receptors in Mediating Systemic Nicotine Effects on Dopamine Release, Locomotion, and Reinforcement

Gotti¹,

Guiducci²,

Tedesco³

et al. 2010

J. Neurosci.

209

236

View full text Add to dashboard Cite

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“…Acquisition of self-administration was performed as described previously with slight modifications (Cohen et al, 2002(Cohen et al, , 2003.…”

Section: Drugsmentioning

confidence: 99%

“…They were then injected with nicotine (0.6 mg/kg, s.c.) and placed in the activity cages for 30 min. This procedure reduced basal level of activity to make the test more suitable to display nicotine-induced hyperactivity (Cohen et al, 2003). Rats that reached 100 photocell interrupts during the habituation period and an increase in locomotor activity of at least 80 photocell interrupts after nicotine injection were selected for nicotine self-administration.…”

Section: Locomotor Screenmentioning

confidence: 99%

Nicotine-Associated Cues Maintain Nicotine-Seeking Behavior in Rats Several Weeks after Nicotine Withdrawal: Reversal by the Cannabinoid (CB1) Receptor Antagonist, Rimonabant (SR141716)

Cohen

Perrault

Griebel

et al. 2004

Neuropsychopharmacol

229

176

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Conditioned stimuli are important for nicotine dependence and may trigger craving and relapse after prolonged nicotine abstinence. However, little is known about the pharmacology of this process. Among the systems that have been shown to play a role in drugseeking behavior is the endocannabinoid transmission. Therefore, the present study examined the resistance to extinction of drugseeking behavior elicited by nicotine-associated environmental stimuli and the effects of the selective CB 1 cannabinoid antagonist rimonabant (SR141716) on the reinforcing effects of nicotine-related stimuli. Rats were trained to self-administer nicotine (0.03 mg/kg/ injection, i.v.) under conditions in which responding was reinforced jointly by response-contingent nicotine injections and stimuli (light and tone). After self-administration acquisition, nicotine was withdrawn and lever pressing was only reinforced by contingent presentation of the audiovisual stimuli. Under such a condition, responding persisted for 3 months, following which nonpresentation of the cues produced a progressive extinction of responding. As expected, rats trained to lever-press for saline injections paired with the audiovisual stimuli did not acquire the self-administration. These findings indicate that the cues required learned association with nicotine to acquire reinforcing properties and to function as conditioned reinforcers. When administered 1 month following nicotine withdrawal, rimonabant (1 mg/kg, i.p.) decreased conditioned behavior. These results showing the persistence of a nicotine-conditioned behavior are congruent with the role of nicotine-related environmental stimuli in nicotine craving in abstinent smokers. Rimonabant, which has been shown previously to reduce nicotine self-administration, may be effective not only as an aid for smoking cessation but also in the maintenance of abstinence.

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“…1 A). A novel selective ␣4␤2 partial agonist, SSR591813 (Cohen et al, 2003), was compared with nicotine to assess its ability to elicit glutamate release from thalamocortical synapses, as shown in Figure 1 B.…”

Section: Electrophysiologymentioning

confidence: 99%

Hypocretin and Nicotine Excite the Same Thalamocortical Synapses in Prefrontal Cortex: Correlation with Improved Attention in Rat

Lambe¹,

Olausson²,

Horst³

et al. 2005

J. Neurosci.

122

103

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Thalamic projections to prefrontal cortex are important for executive aspects of attention. Using two-photon imaging in prefrontal brain slices, we show that nicotine and the wakefulness neuropeptide hypocretin (orexin) excite the same identified synapses of the thalamocortical arousal pathway within the prefrontal cortex. Although it is known that attention can be improved when nicotine is infused directly into the midlayer of the prefrontal cortex in the rat, the effects of hypocretin on attention are not known. The overlap in thalamocortical synapses excited by hypocretin and nicotine and the lack of direct postsynaptic effects prompted us to compare their effects on a sustained and divided attention task in the rat. Similar to nicotine, infusions of hypocretin-2 peptide into the prefrontal cortex significantly improved accuracy under high attentional demand without effects on other performance measures. We show for the first time that hypocretin can improve attentional processes relevant to executive functions of the prefrontal cortex.

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SSR591813, a Novel Selective and Partial α₄β₂ Nicotinic Receptor Agonist with Potential as an Aid to Smoking Cessation

Cited by 113 publications

References 28 publications

Nicotinic Acetylcholine Receptors in the Mesolimbic Pathway: Primary Role of Ventral Tegmental Area α6β2* Receptors in Mediating Systemic Nicotine Effects on Dopamine Release, Locomotion, and Reinforcement

Nicotinic Acetylcholine Receptors in the Mesolimbic Pathway: Primary Role of Ventral Tegmental Area α6β2* Receptors in Mediating Systemic Nicotine Effects on Dopamine Release, Locomotion, and Reinforcement

Nicotine-Associated Cues Maintain Nicotine-Seeking Behavior in Rats Several Weeks after Nicotine Withdrawal: Reversal by the Cannabinoid (CB1) Receptor Antagonist, Rimonabant (SR141716)

Hypocretin and Nicotine Excite the Same Thalamocortical Synapses in Prefrontal Cortex: Correlation with Improved Attention in Rat

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SSR591813, a Novel Selective and Partial α4β2 Nicotinic Receptor Agonist with Potential as an Aid to Smoking Cessation

Cited by 113 publications

References 28 publications

Nicotinic Acetylcholine Receptors in the Mesolimbic Pathway: Primary Role of Ventral Tegmental Area α6β2* Receptors in Mediating Systemic Nicotine Effects on Dopamine Release, Locomotion, and Reinforcement

Nicotinic Acetylcholine Receptors in the Mesolimbic Pathway: Primary Role of Ventral Tegmental Area α6β2* Receptors in Mediating Systemic Nicotine Effects on Dopamine Release, Locomotion, and Reinforcement

Nicotine-Associated Cues Maintain Nicotine-Seeking Behavior in Rats Several Weeks after Nicotine Withdrawal: Reversal by the Cannabinoid (CB1) Receptor Antagonist, Rimonabant (SR141716)

Hypocretin and Nicotine Excite the Same Thalamocortical Synapses in Prefrontal Cortex: Correlation with Improved Attention in Rat

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SSR591813, a Novel Selective and Partial α₄β₂ Nicotinic Receptor Agonist with Potential as an Aid to Smoking Cessation