Effects of central and peripheral nicotinic blockade on human nicotine discrimination |
| |
Authors: | Kenneth A Perkins Mark Sanders Carolyn Fonte Annette S Wilson Wendy White Richard Stiller Dennis McNamara |
| |
Institution: | (1) Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA, US;(2) Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15213, USA, US;(3) Department of Anaesthesia, Children’s Hospital, Pittsburgh, Pennsylvania, USA, US;(4) Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA, US;(5) Western Psychiatric Institute & Clinic, University of Pittsburgh School of Medicine, 3811 O’Hara Street, Pittsburgh, PA 15213, USA e-mail: kperkins@vms.cis.pitt.edu, Fax: +1-412-624-6018, US |
| |
Abstract: | Nicotine produces interoceptive stimulus effects in humans, which may be critical in understanding tobacco use. It has not
yet clearly been demonstrated that discrimination of nicotine, or any drug, in humans is due to its central effects. We compared
effects of mecamylamine (10 mg PO), a central and peripheral nicotine antagonist, on nicotine discrimination with those of
trimethaphan (10–40 μg/kg per min IV), a peripheral nicotine antagonist only, and placebo. Smokers (n = 6) were first trained to reliably discriminate 0 versus 20 μg/kg nicotine by nasal spray and then tested on generalization
of this discrimination across a range of nicotine doses (0, 3, 6, 12, 20 μg/kg) following antagonist/placebo pretreatment.
Nicotine self-administration was also assessed after generalization testing by having participants intermittently choose between
nicotine versus placebo spray. Compared with responding following placebo pre-treatment, discrimination of the highest dose
of nicotine was significantly attenuated following mecamylamine but not trimethaphan. Similar results were observed for some
subjective responses to nicotine. Mecamylamine also tended to increase nicotine self-administration. Consistent with previous
animal studies, these results suggest that discriminative stimulus effects of nicotine in humans are mediated at least in
part by its central effects.
Received: 15 April 1998/Final version: 23 July 1998 |
| |
Keywords: | Nicotine Drug discrimination CNS effect Nicotinic antagonist Subjective effect Reinforcement Self-administration |
本文献已被 PubMed SpringerLink 等数据库收录! |
|