The pedunculopontine tegmental nucleus and the role of cholinergic neuronsin nicotine self-administration in the rat: A correlative neuroanatomical and behavioral study

The objective of this study was to determine whether the pedunculopontine t egmental nucleus plays a role in the maintenance of nicotine self-administr ation, and whether the ascending cholinergic projection from this nucleus t o midbrain dopamine neurons in the ventral tegmental area might be involved . Studies were done with rats trained to self-administer nicotine intraveno usly. Self-administration was examined before and after the pedunculopontin e tegmental nucleus was lesioned with the ethylcholine mustard aziridinium ion, a selective cholinergic toxin. Lesions were assessed qualitatively and quantitatively in histological sections stained for either nicotinamide ad enine dinucleotide phosphate-diaphorase histochemistry to identify choliner gic neurons, or for Nissl. Self-administration was also tested after an acu te manipulation in which microinfusions of the nicotinic cholinergic antago nist dihydro-beta-erythroidine were made into the pedunculopontine tegmentu m. Infusions of neurotoxin into the pedunculopontine tegmentum reduced nicotin e self-administration behaviour when tested weeks later. Toxin treatment re duced the number of cholinergic neurons in the tegmentum, while largely spa ring the non-cholinergic population in this area. Lesions were Limited to t he pedunculopontine area and did not extend to the neighboring laterodorsal tegmental nucleus or to the substantia nigra Acute manipulation of the ped unculopontine tegmental nucleus with microinfusions of dihydro-beta-erythro idine also produced an attenuation of nicotine self-administration. Collectively these data show that the pedunculopontine tegmental nucleus is part of the neuronal circuitry mediating nicotine self-administration, and that the population of cholinergic neurons is likely a critical element. ( C) 2000 IBRO. Published by Elsevier Science Ltd.