Sensitization to cocaine after a single intra-cerebral injection of orphanin FQ/nociceptin.
Orphanin FQ/nociceptin (OFQ/N) has been shown to modulate mesolimbic dopaminergic neurotransmission. Repeated administration of OFQ/N into the ventral tegmental area results in a sensitized locomotor response to subsequent peripheral cocaine administration. The aim of the present study was to examine the potential for OFQ/N to produce a sensitized locomotor response to cocaine after a single intra-VTA administration and to determine if this effect of OFQ/N extrapolates to other points along the mesolimbic or nigrostriatal dopaminergic axes. Bilateral administration of OFQ/N (30 microg/side) into the VTA on day 1 to male Sprague--Dawley rats resulted in an enhanced locomotor response to cocaine (10 mg/kg i.p) administered on day 2. However, OFQ/N (3, 10 and 30 microg per side) administered on day 2, 5 mins prior to the administration of cocaine (10 mg/kg i.p), in animals treated with aCSF or OFQ/N on day 1, similarly blocked the action of cocaine, suggesting that the sensitized response was not due to tolerance to the effect of endogenously released OFQ/N. The administration of OFQ/N into the substantia nigra or nucleus accumbens failed to produce a significant sensitized response to a cocaine challenge 24 h later. A significant increase in cocaine stimulated locomotor response on day 2 was observed after injection of OFQ/N into the striatum on day 1. These results demonstrate the ability of a single intra-VTA or intra-striatal administration of OFQ/N to produce increases in the sensitivity to cocaine and may indicate a role for endogenous OFQ/N systems in regulating responses to psychostimulant drugs.
Narayanan
Shridhar
S
Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, 760, Westwood Plaza, Los Angeles, CA 90024, USA. shridhar@ucla.edu
Lutfy
Kabirullah
K
Maidment
Nigel
N
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004361:Drug Tolerance; D007267:Injections; D007274:Injections, Intraperitoneal; D008032:Limbic System / Q000187:drug effects / Q000502:physiology; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area; D000097629:Nociceptin
D003042:Cocaine; D004298:Dopamine; D018765:Dopamine Uptake Inhibitors; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000097629:Nociceptin