The orphanin receptor agonist RO 64-6198 does not induce place conditioning in rats.
The abuse liability of Ro 64-6198, an orphanin FQ (OFQ) receptor full agonist that exhibits anxiolytic properties, was evaluated using an unbiased conditioned place preference (CPP) paradigm in rats. As OFQ is structurally related to opioid peptides and also exhibits anxiolytic-like properties, the effect of Ro 64-6198 on CPP was compared with those of morphine and alprazolam. We show here that neither Ro 64-6198 nor alprazolam exhibited rewarding or aversive properties, whereas morphine induced a pronounced CPP. These results strengthen the previous finding that Ro 64-6198 lacked abuse liability in a self-stimulation paradigm, suggesting that this new class of anxiolytic drugs is devoid of the risk for potential non-medical use and dependence.
Le Pen
Gwenaëlle
G
Pharma Division, Preclinical CNS Research, F-Hoffmann-La Roche Ltd, PRBN-B 72/141, CH-4070 Basel, Switzerland.
Wichmann
Juergen
J
Moreau
Jean-Luc
JL
Jenck
François
F
D000525:Alprazolam / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists* / Q000502:physiology; D013141:Spiro Compounds / Q000494:pharmacology*; D000094942:Nociceptin Receptor
D000525:Alprazolam; D000701:Analgesics, Opioid; D014151:Anti-Anxiety Agents; D007093:Imidazoles; D009020:Morphine; D011957:Receptors, Opioid; D013141:Spiro Compounds; D000094942:Nociceptin Receptor; C408068:Ro 64-6198; C000722285:Oprl1 protein, rat