title: Muscarinic and nicotinic cholinergic receptor antagonists differentially mediate acquisition of fructose-conditioned flavor preference and quinine-conditioned flavor avoidance in rats.
abstract: Rats display both conditioned flavor preference (CFP) for fructose, and conditioned flavor avoidance (CFA) following sweet adulteration with quinine. Previous pharmacological analyses revealed that fructose-CFP expression was significantly reduced by dopamine (DA) D1 or D2 antagonists, but not NMDA or opioid antagonists. Fructose-CFP acquisition was significantly reduced by DA D1, DA D2 or NMDA antagonists, but not opioid antagonists. Quinine-CFA acquisition was significantly enhanced and prolonged by DA D1, NMDA or opioid, but not DA D2 antagonists. Cholinergic interneurons and projections interact with DA systems in the nucleus accumbens and ventral tegmental area. Further, both muscarinic and nicotinic cholinergic receptor signaling have been implicated in sweet intake and development of food-related preferences. Therefore, the present study examined whether systemic administration of muscarinic (scopolamine: SCOP) or nicotinic (mecamylamine: MEC) cholinergic receptor antagonists mediated fructose-CFP expression, fructose-CFP acquisition and quinine-CFA acquisition. For fructose-CFP expression, rats were trained over 10 sessions with a CS+ flavor in 8% fructose and 0.2% saccharin and a CS- flavor in 0.2% saccharin. Two-bottle choice tests with CS+ and CS- flavors mixed in 0.2% saccharin occurred following vehicle, SCOP (0.1-10mg/kg) and MEC (1-8mg/kg). For fructose-CFP acquisition, six groups of rats received vehicle, SCOP (1 or 2.5mg/kg), MEC (4 or 6mg/kg) or a limited intake vehicle control 0.5h prior to 10 CS+ and CS- training sessions followed by six 2-bottle CS+ and CS- choice tests in 0.2% saccharin. For quinine-CFA acquisition, five groups of rats received vehicle, SCOP (1 or 2.5mg/kg) or MEC (4 or 6mg/kg) 0.5h prior to 8 one-bottle CS- (8% fructose+0.2% saccharin: FS) and CS+ (fructose+saccharin+quinine (0.030%: FSQ) training sessions followed by six 2-bottle CS- and CS+ choice tests in fructose-saccharin solutions. Fructose-CFP expression was significantly reduced by SCOP (2.5-10mg/kg: 65-68%) and MEC (4-8mg/kg: 67-73%) relative to vehicle (89-90%), that occurred only when antagonist doses reduced total saccharin intake but in which CS+ intake was still significantly higher than CS- intake. Fructose-CFP acquisition was eliminated by SCOP at doses of 1 (40-54%) and 2.5 (45-58%)mg/kg, and was accompanied by a failure to observe CS+ and CS- intake differences during testing relative to vehicle (85-92%) and limited control (74-88%) conditions. In contrast, MEC failed to alter fructose-CFP acquisition. Quinine-CFA acquisition was significantly enhanced and prolonged by MEC at 4 (18-24%) and 6 (11-13%) mg/kg relative to vehicle (34-48%). In contrast, SCOP failed to alter quinine-CFA acquisition. These data implicate the cholinergic receptor system in mediating acquisition (learning) of sugar-induced preferences and quinine-induced aversions with muscarinic receptor signaling controlling the former and nicotinic receptor signaling controlling the latter.
authors.affiliation: Behavioral and Cognitive Neuroscience Cluster, Psychology Doctoral Program, The Graduate Center, City University of New York, New York, NY, United States.
authors.forename: Francis M
authors.initials: FM
authors.lastname: Rotella
authors.affiliation: Department of Psychology, Queens College, City University of New York, New York, NY, United States.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Olsson
authors.affiliation: Department of Psychology, Queens College, City University of New York, New York, NY, United States.
authors.forename: Vishal
authors.initials: V
authors.lastname: Vig
authors.affiliation: Department of Psychology, Queens College, City University of New York, New York, NY, United States.
authors.forename: Ira
authors.initials: I
authors.lastname: Yenko
authors.affiliation: Department of Psychology, Queens College, City University of New York, New York, NY, United States.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Pagirsky
authors.affiliation: Department of Psychology, Queens College, City University of New York, New York, NY, United States.
authors.forename: Ilanna
authors.initials: I
authors.lastname: Kohen
authors.affiliation: Department of Psychology, Queens College, City University of New York, New York, NY, United States.
authors.forename: Alon
authors.initials: A
authors.lastname: Aminov
authors.affiliation: Department of Psychology, Queens College, City University of New York, New York, NY, United States.
authors.forename: Trisha
authors.initials: T
authors.lastname: Dindyal
authors.affiliation: Behavioral and Cognitive Neuroscience Cluster, Psychology Doctoral Program, The Graduate Center, City University of New York, New York, NY, United States; Department of Psychology, Queens College, City University of New York, New York, NY, United States. Electronic address: richard.bodnar@qc.cuny.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bodnar
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects*; D005632:Fructose / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D011803:Quinine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000008:administration & dosage / Q000494:pharmacology; D013549:Sweetening Agents / Q000008:administration & dosage / Q000494:pharmacology; D055697:Taste Perception / Q000187:drug effects*
chemical_list: D018712:Analgesics, Non-Narcotic; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D013549:Sweetening Agents; D005632:Fructose; D008464:Mecamylamine; D011803:Quinine; D012601:Scopolamine
keywords: Learning; Mecamylamine; Scopolamine