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A functional dissociation of the anterior and posterior pedunculopontine tegmental nucleus : excitotoxic lesions have differential effects on locomotion and the response to nicotine

Alderson, Helen L and Latimer, Mary P and Winn, Philip (2008) A functional dissociation of the anterior and posterior pedunculopontine tegmental nucleus : excitotoxic lesions have differential effects on locomotion and the response to nicotine. Brain Structure and Function, 213 (1-2). pp. 247-253. ISSN 1863-2653

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Abstract

Excitotoxic lesions of posterior, but not anterior pedunculopontine tegmental nucleus (PPTg) change nicotine self-administration, consistent with the belief that the anterior PPTg (aPPTg) projects to substantia nigra pars compacta (SNC) and posterior PPTg (pPPTg) to the ventral tegmental area (VTA). The VTA is a likely site both of nicotine's reinforcing effect as well as its actions on locomotion. We hypothesized that pPPTg, but not aPPTg lesions, would alter locomotion in response to repeated nicotine administration by virtue of the fact that pPPTg appears to be more closely related to the VTA than is the aPPTg. Following excitotoxic lesions of aPPTg or pPPTg, rats were habituated to experimental procedures. Repeated (seven of each) nicotine (0.4 mg/kg) and saline injections were given following an on-off procedure. Measurement of spontaneous locomotion during habituation showed that aPPTg but not pPPTg lesioned rats were hypoactive relative to controls. Following nicotine, control rats showed locomotor depression for the first 2 days of treatment followed by enhanced locomotion relative to activity following saline treatment. Rats with aPPTg lesions showed a similar pattern, but the pPPTg lesioned rats showed no locomotor depression following nicotine treatment. These data confirm the role of the pPPTg in nicotine's behavioural effects--including the development of sensitization--and demonstrate for the first time that excitotoxic lesions of the aPPTg but not pPPTg generate a deficit in baseline activity. The finding that anterior but not posterior PPTg affects motor activity has significance for developing therapeutic strategies for Parkinsonism using deep brain stimulation aimed here.

Item type: Article
ID code: 32777
Keywords: analysis of variance, animals, excitatory amino acid agonists, ibotenic acid, microinjections, motor activity , nicotine, nicotinic agonists, pedunculopontine tegmental nucleus, rats, Therapeutics. Pharmacology, Anatomy, Neuroscience(all), Histology
Subjects: Medicine > Therapeutics. Pharmacology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Pure Administrator
    Date Deposited: 24 Aug 2011 10:45
    Last modified: 05 Sep 2014 10:18
    URI: http://strathprints.strath.ac.uk/id/eprint/32777

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