Philip B Clarke

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1--Rats were tested for locomotor activity in photocell cages, for 80 min starting immediately after subcutaneous injection of (-)-nicotine bitartrate or 0.9% w/v NaCl solution (saline). In non-tolerant subjects, nicotine (0.1 to 0.4 mg/kg base) depressed activity and induced ataxia in the first 20 min, but increased activity later in the session; these(More)
Tests of locomotor activity (photocell cages) were used to investigate the development of tolerance to nicotine in rats. Repeated exposure to the apparatus did not influence the rate at which tolerance was acquired. Comparisons of (+)-nicotine (0.4-1.6 mg kg-1, s.c.) and (-)-nicotine (0.1-0.4 mg kg-1, s.c.) in tolerant rats showed that the (-)-isomer was at(More)
The modulatory influence of nicotinic acetylcholine receptor (nAChRs) on thalamocortical transmission was characterized in the prelimbic area (PrL) of the rat prefrontal cortex. In the first experiment, rats received a unilateral excitotoxic lesion centred on the mediodorsal thalamic nucleus (MD), and were sacrificed 1 week later. The lesion resulted in a(More)
L-Nicotine stimulates locomotor activity in rats which have had prior experience of the drug. The present study investigated whether this behavioral effect is related to activation of the mesolimbic dopamine system. In the first experiment, l-nicotine (0.2-0.8 mg/kg s.c.) stimulated locomotor activity and increased dopamine utilization in the olfactory(More)
Rats received unilateral injections of 6-hydroxydopamine into the medial forebrain bundle, resulting in an ipsilateral loss of striatal dopamine and of dopaminergic perikarya. A concomitant reduction of displaceable tritiated nicotine binding was observed autoradiographically in the ipsilateral substantia nigra, ventral tegmental area, striatum, nucleus(More)
Dopaminergic neurons of the substantia nigra pars compacta are excited by nicotine and acetylcholine, and possess both high-affinity nicotine binding sites and intense acetylcholinesterase activity, consistent with a cholinoceptive role. A probable source of cholinergic afferents is the pedunculopontine nucleus, which forms part of a prominent group of(More)
Extracellular recordings of single unit activity were made in the substantia nigra (SN) of chloral hydrate-anaesthetized rats. Dopaminergic neurones of the pars compacta (SNC) were stimulated by (-)-nicotine bitartrate (1.0 mg kg-1) given subcutaneously (s.c.). This action was prevented by the secondary amine mecamylamine HCl (2.0 mg kg-1 i.v.) but not by a(More)
Three radioligands have been commonly used to label putative nicotinic cholinoceptors in the mammalian central nervous system: the agonists [3H]nicotine and [3H]acetylcholine ([3H]ACh--in the presence of atropine to block muscarinic receptors), and the snake venom extract, [125I]-alpha-bungarotoxin([125I]BTX), which acts as a nicotinic antagonist at the(More)
Several drugs of abuse, including nicotine, are thought to exert their reinforcing effects through actions on the mesolimbic dopamine system. Animal and human studies suggest that chronic administration of addictive drugs may lead to impaired dopamine neurotransmission in the nucleus accumbens. We measured D1 receptor density in 11 smokers and 18 nonsmokers(More)
The cholinergic innervation of the interpeduncular nucleus (IPN) is wholly extrinsic and is greatly attenuated by bilateral habenular destruction. We describe changes in the labeling of putative nicotinic receptors within this nucleus at 3, 5, or 11 days after bilateral habenular lesions. Adjacent tissue sections of the rat IPN were utilized for 3H-nicotine(More)