title: Effects of the dopamine stabilizers (S)-(-)-OSU6162 and ACR16 on prolactin secretion in drug-naive and monoamine-depleted rats.
abstract: Dopaminergic stabilizers may be conceptualized as drugs with normalizing effects on dopamine-mediated behaviours and neurochemical events. (S)-(-)-OSU6162 (OSU6162) and ACR16 are two structurally related compounds ascribed such properties, principally because of their stabilizing effects on motor activity in rodents. Reports in the literature indicate possible partial D2 receptor agonist effects using various in vitro systems. This study aimed to measure D2 receptor antagonist and agonist effects of OSU6162 and ACR16 in vivo. To address this, we have studied the effects of both compounds on prolactin secretion in drug-naive and dopamine-depleted rats; dopamine depletion was induced by pretreatment with reserpine plus α-methyl-DL: -p-tyrosine. We find that OSU6162 and ACR16 both stimulate prolactin secretion in drug-naive rats with OSU6162 being considerably more potent and efficacious. Both compounds show a non-significant trend towards reversal of the increased secretion caused by dopamine depletion, whereas the D2 receptor antagonist haloperidol further increased prolactin secretion. Thus, this study suggests that OSU6162 and ACR16 act as D2 receptor antagonists under normal conditions in vivo, possibly with minor agonist effects in a state of dopamine depletion.
authors.affiliation: Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden. rungjp@gmail.com
authors.forename: Johan P
authors.initials: JP
authors.lastname: Rung
authors.forename: Emilia
authors.initials: E
authors.lastname: Rung
authors.forename: Anette M
authors.initials: AM
authors.lastname: Johansson
authors.forename: Kjell
authors.initials: K
authors.lastname: Svensson
authors.forename: Arvid
authors.initials: A
authors.lastname: Carlsson
authors.forename: Maria L
authors.initials: ML
authors.lastname: Carlsson
mesh_terms: D000818:Animals; D000068180:Aripiprazole; D004298:Dopamine / Q000172:deficiency*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D006966:Hyperprolactinemia / Q000097:blood / Q000139:chemically induced; D052682:Lactotrophs / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008781:Methyltyrosines / Q000008:administration & dosage / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood* / Q000378:metabolism; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D012110:Reserpine / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D008781:Methyltyrosines; D010879:Piperazines; D010880:Piperidines; D015363:Quinolones; D017448:Receptors, Dopamine D2; C109513:OSU 6162; C022260:alpha-methyltyrosine methyl ester; D000068180:Aripiprazole; D012110:Reserpine; D011388:Prolactin; C026539:preclamol; C483720:pridopidine; D006220:Haloperidol; D004298:Dopamine