The sigma ligand rimcazole activates noradrenergic neurons projecting to the paraventricular nucleus and increases corticosterone secretion in rats.
Intraperitoneal injection of rimcazole, a sigma ligand, into male rats increased plasma concentrations of corticosterone in a dose- and time-related fashion. Concurrently, rimcazole increased concentrations of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in the paraventricular nucleus (PVN) of the hypothalamus, suggesting that the drug activates noradrenergic neurons terminating in this nucleus. This latter suggestion was confirmed by the finding that rimcazole also increased concentrations of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) in the PVN. Pentazocine, a sigma ligand was without effect per se, but blocked the ability of rimcazole to increase concentrations of MHPG in the PVN and corticosterone in plasma. Taken together, these results suggest that rimcazole activates noradrenergic neurons projecting to the PVN via a mechanism involving sigma binding sites, and this action may be responsible for the ability of this drug to increase secretion of corticosterone.
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824, USA.
M J
MJ
Eaton
K J
KJ
Lookingland
K E
KE
Moore
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D010423:Pentazocine / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017480:Receptors, sigma / Q000819:agonists / Q000502:physiology*; D012680:Sensitivity and Specificity
D014150:Antipsychotic Agents; D002227:Carbazoles; D017480:Receptors, sigma; D015102:3,4-Dihydroxyphenylacetic Acid; D008734:Methoxyhydroxyphenylglycol; C034931:rimcazole; D010423:Pentazocine; D004298:Dopamine; D003345:Corticosterone; D009638:Norepinephrine