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The stereotypy-inducing and OCD-like effects of chronic 'binge' cocaine are modulated by distinct subtypes of nicotinic acetylcholine receptors.

Metaxas, A, Keyworth, HL, Yoo, JH, Chen, Y, Kitchen, I and Bailey, A (2012) The stereotypy-inducing and OCD-like effects of chronic 'binge' cocaine are modulated by distinct subtypes of nicotinic acetylcholine receptors. Br J Pharmacol.

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Background and purpose: High rates of cigarette smoking occur in cocaine dependent individuals, reflecting an involvement of nicotinic acetylcholine receptors (nAChRs) in cocaine-elicited behaviour. This study was designed to parse the contribution of different nAChR subtypes to the behavioural and neurochemical effects of chronic cocaine treatment. Experimental approach: Cocaine (15 mg/kg, i.p.) was administered to male C57BL/6J mice in a chronic 'binge' paradigm, with and without the co-administration of the α7 preferring antagonist methyllycaconitine (MLA; 5 mg/kg; i.p.) or the β2* nAChR antagonist dihydro-β-erythroidine (DHßE; 2 mg/kg. i.p.). Quantitative autoradiography was used to examine the impact of cocaine exposure on α7 and α4β2* nAChRs, and on the high-affinity choline transporter. Key results: MLA+cocaine administration induced an intense self-grooming behaviour, indicating a likely role for α7 nAChRs in modulating this anxiogenic, compulsive-like effect of cocaine. In the major island of Calleja, a key area of action for neuroleptics, MLA+cocaine reduced choline-transporter binding compared to cocaine (±DHßE) administration. DHßE treatment prevented the induction of stereotypy sensitisation to cocaine, but prolonged locomotor sensitisation, implicating heteromeric β2* nAChRs in the neuroadaptations mediating cocaine-induced behavioural sensitisation. 'Binge' cocaine treatment region-specifically increased α4β2* nAChR binding in the midbrain dopaminergic regions: ventral tegmental area and substantia nigra pars compacta. Conclusions and implications: We show a differential, subtype-selective contribution of nAChRs to the behavioural and neurochemical sequelae of chronic cocaine administration. These data support the clinical utility of targeting specific nAChR subtypes for the alleviation of cocaine-abuse symptomatology. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Item Type: Article
Authors :
Metaxas, A
Keyworth, HL
Yoo, JH
Chen, Y
Kitchen, I
Bailey, A
Date : 9 May 2012
Identification Number : 10.1111/j.1476-5381.2012.02023.x
Depositing User : Symplectic Elements
Date Deposited : 28 Mar 2017 14:10
Last Modified : 31 Oct 2017 14:47

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