Effects of mood stabilizers on brain reward processes in rats: studies using the intracranial self-stimulation paradigm.
Bipolar disorder is characterized by dysregulated motivation and increased hedonistic drive. d-Amphetamine induces manic symptoms in humans and exacerbates mania in bipolar disorder patients, effects that are counteracted by mood stabilizers. We utilized intracranial self-stimulation (ICSS) to examine how lithium (LiCl), valproate (VPA) or their combination that is commonly used in the clinic affect brain reward function in rats, and how these drugs affect d-amphetamine's reward-facilitating effects. Acute intraperitoneal (i.p.) administration of LiCl (100, 200 mg/kg), VPA (400 mg/kg) or combined administration of subthreshold doses of LiCl (50 mg/kg) and VPA (200 mg/kg) increased ICSS thresholds. LiCl (100 mg/kg) and combined administration of LiCl and VPA (50 and 200 mg/kg), but not VPA alone (200, 400 mg/kg), attenuated d-amphetamine's reward-facilitating effects. These results suggest that ICSS combined with d-amphetamine constitutes a useful model to explore the elation and increased hedonistic drive observed in bipolar patients and ultimately help to identify novel pharmacotherapies for bipolar disorder.
Mavrikaki
Maria
M
University of Crete, School of Social Sciences, Department of Psychology, Laboratory of Behavioral Neuroscience, 74100 Rethymno, Crete, Greece.
Nomikos
George G
GG
Panagis
George
G
D000704:Analysis of Variance; D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage*; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D003216:Conditioning, Operant / Q000187:drug effects*; D003913:Dextroamphetamine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004338:Drug Combinations; D018021:Lithium Chloride / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012646:Self Administration / Q000379:methods; D014635:Valproic Acid / Q000008:administration & dosage
D018692:Antimanic Agents; D000697:Central Nervous System Stimulants; D004338:Drug Combinations; D014635:Valproic Acid; D018021:Lithium Chloride; D003913:Dextroamphetamine