title: The Aversive Agent Lithium Chloride Suppresses Phasic Dopamine Release Through Central GLP-1 Receptors.
abstract: Unconditioned rewarding stimuli evoke phasic increases in dopamine concentration in the nucleus accumbens (NAc) while discrete aversive stimuli elicit pauses in dopamine neuron firing and reductions in NAc dopamine concentration. The unconditioned effects of more prolonged aversive states on dopamine release dynamics are not well understood and are investigated here using the malaise-inducing agent lithium chloride (LiCl). We used fast-scan cyclic voltammetry to measure phasic increases in NAc dopamine resulting from electrical stimulation of dopamine cell bodies in the ventral tegmental area (VTA). Systemic LiCl injection reduced electrically evoked dopamine release in the NAc of both anesthetized and awake rats. As some behavioral effects of LiCl appear to be mediated through glucagon-like peptide-1 receptor (GLP-1R) activation, we hypothesized that the suppression of phasic dopamine by LiCl is GLP-1R dependent. Indeed, peripheral pretreatment with the GLP-1R antagonist exendin-9 (Ex-9) potently attenuated the LiCl-induced suppression of dopamine. Pretreatment with Ex-9 did not, however, affect the suppression of phasic dopamine release by the kappa-opioid receptor agonist, salvinorin A, supporting a selective effect of GLP-1R stimulation in LiCl-induced dopamine suppression. By delivering Ex-9 to either the lateral or fourth ventricle, we highlight a population of central GLP-1 receptors rostral to the hindbrain that are involved in the LiCl-mediated suppression of NAc dopamine release.
authors.affiliation: Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Fortin
authors.affiliation: Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA, USA.
authors.forename: Elena H
authors.initials: EH
authors.lastname: Chartoff
authors.affiliation: Department of Psychology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Mitchell F
authors.initials: MF
authors.lastname: Roitman
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D045785:Diterpenes, Clerodane / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D000067757:Glucagon-Like Peptide-1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D011619:Psychotropic Drugs / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000378:metabolism; D012201:Reward; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D045785:Diterpenes, Clerodane; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D011619:Psychotropic Drugs; D017473:Receptors, Opioid, kappa; D018021:Lithium Chloride; C090499:salvinorin A; D004298:Dopamine