title: GTS-21, a mixed nicotinic receptor agonist/antagonist, does not affect the nicotine cue.
abstract: Identification of nicotinic receptor subtypes involved in nicotine dependence is required for guiding the design of more selective antagonists capable of blocking the nicotine cue and nicotine self-administration. Due to the multiplicity of nicotinic receptors in the mammalian brain, selective agonists and antagonists are needed to assess the functional involvement of a particular subtype in vivo. Only recently have a few nicotinic receptor subtype-selective antagonists and agonists been identified. GTS-21 (also known as DMBX-anabaseine) is the only agent so far reported that selectively stimulates the alpha7 nicotinic receptor. Here GTS-21 was used to assess the possible mediation of the nicotine cue by this receptor subtype. Long-Evans rats were trained to discriminate between presession administration of 0.10 or 0.40 mg/kg (-)-nicotine bitartrate and its vehicle. GTS-21 did not substitute for nicotine, as all subjects consistently chose the vehicle lever after GTS-21 substitution. In another experiment, different doses of GTS-21 were administered prior to nicotine administration to investigate whether GTS-21 would antagonize the nicotine cue. Such was not the case. The lack of effect of GTS-21 upon the nicotine cue is consistent with the notion that the cue is mediated by nicotinic receptors other than the alpha7 receptor.
authors.affiliation: Department of Psychology, University of Florida, Gainesville 32611-2250, USA.
authors.forename: F
authors.initials: F
authors.lastname: van Haaren
authors.forename: K G
authors.initials: KG
authors.lastname: Anderson
authors.forename: S C
authors.initials: SC
authors.lastname: Haworth
authors.forename: W R
authors.initials: WR
authors.lastname: Kem
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000691:Anabasine / Q000494:pharmacology; D000818:Animals; D001392:Azocines; D001597:Benzylidene Compounds / Q000494:pharmacology*; D003463:Cues; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D005795:Generalization, Stimulus / Q000187:drug effects; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011807:Quinolizines; D051381:Rats; D020318:Rats, Long-Evans; D011978:Receptors, Nicotinic / Q000187:drug effects*; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000093843:Quinolizidine Alkaloids
chemical_list: D000470:Alkaloids; D000691:Anabasine; D001392:Azocines; D001597:Benzylidene Compounds; D009538:Nicotine; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D011807:Quinolizines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579165:Chrna7 protein, rat; C004712:cytisine; D000093843:Quinolizidine Alkaloids; C088936:3-(2,4-dimethoxybenzylidene)anabaseine