title: Sigma 1 receptor subtype is involved in the facilitation of cortical dopaminergic transmission in the rat brain.
abstract: Our previous studies have shown that three sigma (sigma) receptor ligands, (+)-N-allylnormetazocine ((+)-SKF-10,047), (+/-)-pentazocine and 1,3-di(2-tolyl)guanidine (DTG) differently regulated the dopamine (DA) transmission in the rat brain. In the present study, we attempted to clarify the role of sigma 1 receptor subtype in the regulation of DA transmission using a novel and selective sigma 1 receptor agonist, 1-(3,4-dimethoxyphenethyl)-4(3-phenylpropyl)piperazine dihydrochloride (SA4503) in the rat brain. Acute administration of SA4503 (1.0 mg/kg, p.o.) significantly increased DA and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the rat frontal cortex, but not in the other six regions, hippocampus, striatum, midbrain, cerebellum, medulla/pons and hypothalamus. The increase of cortical DA level elicited by SA4503 was fully reversed by N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine (NE-100) (0.25 mg/kg, p.o.), a putative sigma 1 receptor antagonist. In addition, SA4503 (1.0 mg/kg, p.o.) showed an increase of cortical L-3,4-dihydroxyphenylalanine (L-DOPA) accumulation under the inhibition of dopa decarboxylase activity with m-hydrobenzylhydrazine (NSD-1015), suggesting that SA4503 has activated the cortical DA synthesis rate. These results suggest that the sigma 1 receptor subtype plays an important role in the facilitation of cortical DA transmission. In addition, this phenomenon is partially involved in the augmentation of DA synthesis rate.
authors.affiliation: Central Research Laboratories, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Matsuno
authors.forename: M
authors.initials: M
authors.lastname: Murai
authors.forename: S
authors.initials: S
authors.lastname: Mita
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D005625:Frontal Lobe / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000819:agonists / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D010879:Piperazines; D017480:Receptors, sigma; D015102:3,4-Dihydroxyphenylacetic Acid; C101789:SA 4503; D004298:Dopamine