Propranolol attenuates haloperidol-induced Fos expression in discrete regions of rat brain: possible brain regions responsible for akathisia.
Neuroleptics induce several extra-pyramidal side effects, such as akathisia, acute dystonia and parkinsonism. Although recently developed atypical neuroleptics ameliorate some of these side effects, akathisia remains a common and severely distressing adverse reaction. Several drugs are reported to be of clinical use for the pharmacological treatment of akathisia. In particular, the beta-adrenoceptor blocker, propranolol, has been widely used for the treatment of akathisia, but it does not ameliorate other extra-pyramidal side effects. To identify the neural substrates of akathisia, we investigated the effects of propranolol on haloperidol-induced Fos expression in rat brain. Haloperidol (1 mg/kg) induced Fos-positive nuclei in several regions of the brain, including the cingulate cortex area 3, piriform cortex nucleus accumbens, caudate-putamen, ventral lateral septum and parietal cortex. Pretreatment with propranolol (5 mg/kg) reduced the number of Fos-positive nuclei in the cingulate cortex area 3, the piriform cortex and area 1 of the parietal cortex. Injection of vehicle by itself tended to increase Fos expression in the cingulate cortex area 3 and the piriform cortex. Considering the functions of these brain regions, we speculate that the most plausible neural framework for haloperidol-induced akathisia involves area I of the parietal cortex, but possible roles for the cingulate cortex area 3 and the piriform cortex cannot be ruled out.
Ohashi
K
K
Department of Neuropsychiatry, Okayama University Medical School, Japan.
Hamamura
T
T
Lee
Y
Y
Fujiwara
Y
Y
Kuroda
S
S
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001931:Brain Mapping; D004338:Drug Combinations; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D011433:Propranolol / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011595:Psychomotor Agitation / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D000319:Adrenergic beta-Antagonists; D014150:Antipsychotic Agents; D004338:Drug Combinations; D016760:Proto-Oncogene Proteins c-fos; D011433:Propranolol; D006220:Haloperidol