Acute buspirone abolishes the expression of behavioral dopaminergic supersensitivity in mice.
Previous studies have shown that rats withdrawn from long-term treatment with dopamine receptor blockers exhibit dopaminergic supersensitivity, which can be behaviorally evaluated by enhanced general activity observed in an open-field. Recently, it has been reported that co-treatment with the non-benzodiazepine anxiolytic buspirone attenuates the development of haloperidol-induced dopaminergic supersensitivity measured by open-field behavior of rats. The aims of the present study were: 1) to determine, as previously reported for rats, if mice withdrawn from long-term neuroleptic treatment would also develop dopaminergic supersensitivity using open-field behavior as an experimental paradigm, and 2) to examine if acute buspirone administration would attenuate the expression of this behavioral dopaminergic supersensitivity. Withdrawal from long-term haloperidol treatment (2.5 mg/kg, once daily, for 20 days) induced a significant (30%) increase in ambulation frequency (i.e., number of squares crossed in 5-min observation sessions) but did not modify rearing frequency or immobility duration in 3-month-old EPM-M1 male mice observed in the open-field apparatus. Acute intraperitoneal injection of buspirone (3.0 and 10 but not 1.0 mg/kg, 12-13 animals per group) 30 min before open-field exposure abolished the increase in locomotion frequency induced by haloperidol withdrawal. These data suggest that the open-field behavior of mice can be used to detect dopaminergic supersensitivity, whose expression is abolished by acute buspirone administration.
Queiroz
C M T
CM
Departamento de Farmacologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
Alcântara
F B
FB
Yagüe
A M L
AM
Bibancos
T
T
Frussa-Filho
R
R
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002065:Buspirone / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004342:Drug Hypersensitivity / Q000209:etiology*; D004347:Drug Interactions; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D013239:Stereotyped Behavior / Q000187:drug effects
D014151:Anti-Anxiety Agents; D018492:Dopamine Antagonists; D006220:Haloperidol; D002065:Buspirone; D004298:Dopamine