Acute effects of sigma ligands on the electrophysiological activity of rat nigrostriatal and mesoaccumbal dopaminergic neurons.
The effects of acute i.v. administration of several sigma ligands on the single-unit activity of nigrostriatal and mesoaccumbal dopaminergic (DA) neurons were evaluated in chloral hydrate-anesthetized rats. DTG (1,3-di(o-tolyl)guanidine) did not alter DA neuronal activity at nontoxic doses and JO 1784 [(+)-N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1-ethylbut-3-en-1-+ ++ylamine] was inactive. (+)-Pentazocine was more effective in increasing mesoaccumbal vs. nigrostriatal DA cell firing rates. BMY 14802(alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine-but anol) dose-dependently increased DA cell firing rate in both populations. The inhibition of nigrostriatal DA cell firing rate by (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(+)-3-PPP] was reversed by (-)-eticlopride and (+)-but not (-)-butaclamol, which supports previous evidence that (+)-3-PPP-induced inhibition is due to the DA agonist properties of the drug. From what is known of the pharmacological properties of these compounds, it is concluded that acute sigma receptor occupation does not markedly alter the firing rate of DA neurons. The dose-response curve for inhibition of nigrostriatal DA neuronal activity by the D2 DA agonist, quinpirole, was shifted to the right tenfold by BMY 14802 pretreatment (8 mg/kg, i.v.) and twofold by (+)-pentazocine (8 mg/kg, i.v.), but was not changed by DTG (2 mg/kg, i.v.). It is concluded that the marked effects of certain sigma ligands on DA cell electrophysiology are likely due to their non-sigma properties.
Zhang
J
J
Department of Psychiatry, Wayne State University School of Medicine, Detroit, Michigan 48201.
Chiodo
L A
LA
Wettstein
J G
JG
Junien
J L
JL
Freeman
A S
AS
D000818:Animals; D002421:Caudate Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D008024:Ligands; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011699:Putamen / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*; D017480:Receptors, sigma; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D008024:Ligands; D011957:Receptors, Opioid; D017480:Receptors, sigma; D004298:Dopamine