title: Exendin-4 decreases amphetamine-induced locomotor activity.
abstract: Glucagon-like peptide-1 (GLP-1) is released in response to nutrient ingestion and is a regulator of energy metabolism and consummatory behaviors through both peripheral and central mechanisms. The GLP-1 receptor (GLP-1R) is widely distributed in the central nervous system, however little is known about how GLP-1Rs regulate ambulatory behavior. The abused psychostimulant amphetamine (AMPH) promotes behavioral locomotor activity primarily by inducing the release of the neurotransmitter dopamine. Here, we identify the GLP-1R agonist exendin-4 (Ex-4) as a modulator of behavioral activation by AMPH. We report that in rats a single acute administration of Ex-4 decreases both basal locomotor activity as well as AMPH-induced locomotor activity. Ex-4 did not induce behavioral responses reflecting anxiety or aversion. Our findings implicate GLP-1R signaling as a novel modulator of psychostimulant-induced behavior and therefore a potential therapeutic target for psychostimulant abuse.
authors.affiliation: Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN 37232, USA. kevin.erreger@vanderbilt.edu
authors.forename: Kevin
authors.initials: K
authors.lastname: Erreger
authors.forename: Adeola R
authors.initials: AR
authors.lastname: Davis
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Poe
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Greig
authors.forename: Gregg D
authors.initials: GD
authors.lastname: Stanwood
authors.forename: Aurelio
authors.initials: A
authors.lastname: Galli
mesh_terms: D000661:Amphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D001007:Anxiety / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000502:physiology; D000067757:Glucagon-Like Peptide-1 Receptor; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000819:agonists / Q000187:drug effects; D014688:Venoms / Q000494:pharmacology*
chemical_list: D018692:Antimanic Agents; D000697:Central Nervous System Stimulants; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D000661:Amphetamine; D018021:Lithium Chloride