title: Morphine sensitization as a model of mania: comparative study of the effects of repeated lithium or carbamazepine administration.
abstract: Repeated unavoidable stress induces in rats decreased reactivity to avoidable stressors and an anhedonia-like condition that are reverted by long-term antidepressant treatments and regarded as models of core symptoms of depression. Morphine-sensitized rats present resilience to stress-induced behavioral deficits and, if hyporeactivity to stress models a depressive symptom, stress resistance can be regarded as a manic symptom. This hypothesis is supported by the observation that long-term lithium administration reinstates sensitivity to stress in sensitized rats. The first aim of the study was to examine the effects of carbamazepine, a standard antimanic treatment, on the stress resilience of sensitized rats, to further characterize morphine sensitization as a model of manic symptom. Carbamazepine administration abolished stress resilience but did not interfere with the expression of sensitization. The second aim of the study was to assess whether repeated carbamazepine treatment affected the dopaminergic and behavioral responses to a natural reward, a palatable food (vanilla sugar, VS), in non food-deprived sensitized and control rats and compare these possible effects with those of repeated lithium administration. Control and sensitized rats showed increased extraneuronal dopamine levels in the nucleus accumbens shell after VS consumption and competence to acquire an instrumental VS-sustained appetitive behavior (VAB). Repeated carbamazepine treatment abolished the dopaminergic response to VS consumption and disrupted the competence to acquire VAB in control rats. Lithium-treated rats showed a dopaminergic response to VS and easily acquired the appetitive behavior. In sensitized rats, neither carbamazepine nor lithium administration interfered with the dopaminergic response to VS and the acquisition of VAB. In summary, the effect of carbamazepine on the stress resilience of sensitized rats further supported the hypothesis that morphine sensitization might model some symptoms of mania. Moreover, in control rats carbamazepine treatment elicited an anhedonia-like condition that clearly distinguished the effects of this drug from those of lithium.
authors: Department of Neuroscience, University of Siena, Via Moro, 4, 53100 Siena, Italy. grappi2@unisi.it
authors: Silvia
authors: S
authors: Grappi
authors: Giovanna
authors: G
authors: Marchese
authors: Maria Elena
authors: ME
authors: Secci
authors: Maria Graziella
authors: MG
authors: De Montis
authors: Carla
authors: C
authors: Gambarana
authors: Simona
authors: S
authors: Scheggi
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D018692:Antimanic Agents / Q000494:pharmacology*; D001070:Appetitive Behavior / Q000187:drug effects; D001714:Bipolar Disorder / Q000139:chemically induced* / Q000523:psychology*; D001923:Brain Chemistry / Q000187:drug effects; D002220:Carbamazepine / Q000494:pharmacology*; D059333:Central Nervous System Sensitization / Q000187:drug effects*; D002755:Choice Behavior / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004924:Escape Reaction / Q000187:drug effects; D005502:Food; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000494:pharmacology*; D009714:Nucleus Accumbens; D051381:Rats; D017207:Rats, Sprague-Dawley; D055500:Resilience, Psychological / Q000187:drug effects; D013315:Stress, Psychological / Q000523:psychology
chemical_list: D000701:Analgesics, Opioid; D000927:Anticonvulsants; D018692:Antimanic Agents; D002220:Carbamazepine; D009020:Morphine; D018021:Lithium Chloride; D004298:Dopamine