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Reinforcing effects of nicotine microinjections into the ventral tegmental area of mice: dependence on cholinergic nicotinic and dopaminergic D1 receptors.

Abstract : We used an intracranial self-administration (ICSA) procedure to assess the involvement of the ventral tegmental area (VTA) nicotinic receptors in the rewarding effects of nicotine. We then challenged intra-VTA nicotine self-administration via systemic or local injections of dopamine (DA)-D1 and nicotinic receptor antagonists. C57BL/6J mice were stereotaxically implanted unilaterally with a guide cannula above the VTA. After 1 week of recovery, mice were allowed to discriminate between two arms of a Y-maze over seven daily sessions, one arm being reinforced by intracranial nicotine microinjection. Mice exhibited nicotine self-administration at both doses tested, i.e. 10 ng (21.6 pmol) and 100 ng (216 pmol)/50-nl injection. In contrast, mice receiving a 216-pmol nicotine dose 0.8 mm above VTA performed at chance level. Once the ICSA response was acquired, systemic pretreatment with the DA-D1 receptor antagonist SCH 23390 (25 microg/kg i.p.) or co-infusion of the nAChR antagonist DHbetaE with nicotine disrupted ICSA. Replacement of SCH 23390 by vehicle, or withdrawal of DHbetaE from nicotine/DHbetaE mixed solutions led to recovery of intra-VTA nicotine self-administration. We conclude that nicotinic receptors in the VTA, presumably alpha4beta2 nAChRs are critically to mediate the rewarding effects of nicotine and that DA-D1 receptors are also directly implicated.
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Submitted on : Tuesday, July 10, 2007 - 4:44:01 PM
Last modification on : Wednesday, October 14, 2020 - 4:09:51 AM

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Vincent David, Morgane Besson, Jean-Pierre Changeux, Sylvie Granon, Pierre Cazala. Reinforcing effects of nicotine microinjections into the ventral tegmental area of mice: dependence on cholinergic nicotinic and dopaminergic D1 receptors.. Neuropharmacology, Elsevier, 2006, 50 (8), pp.1030-40. ⟨10.1016/j.neuropharm.2006.02.003⟩. ⟨pasteur-00161455⟩

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