Kappa-opioid agonist U69593 potentiates locomotor sensitization to the D2/D3 agonist quinpirole: pre- and postsynaptic mechanisms.
To assess whether the development and expression of behavioral sensitization to the dopamine D2/D3 agonist quinpirole (QNP) is influenced by coadministration of the kappa opioid receptor agonist U69593, rats received every 3-4 days for a total of 10 treatments an injection of U69593 (0.3 mg/kg) together with an injection of either a postsynaptic (0.5 mg/kg) or a presynaptic dose of QNP (0.05 mg/kg); locomotor activity was measured after each treatment. Control rats were injected as appropriate with QNP, U69593, and vehicle/saline. Following chronic treatment, dose-response profiles to QNP were obtained to assess the expression of sensitization; the effect of U69593 on locomotor activity in animals already sensitized to QNP was also assessed. Results showed that cotreatment of U69593 with a postsynaptic dose of QNP doubled the speed and magnitude of sensitization to QNP, while U69593 cotreatment with a presynaptic dose of QNP switched the effects of QNP from locomotor depression to locomotor sensitization. However, U69593 cotreatment with a presynaptic dose of QNP changed a different set of measures of sensitization than did cotreatment with a postsynaptic dose of the dopamine agonist. Together, findings suggest that sensitization to QNP is not a unitary phenomenon but has components that are relatively independent, mediated by distinct pre- and postsynaptic mechanisms and modulated by kappa receptor activity.
Perreault
Melissa L
ML
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
Graham
Dawn
D
Bisnaire
Liane
L
Simms
Jennifer
J
Hayton
Scott
S
Szechtman
Henry
H
D000465:Algorithms; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D044482:Benzeneacetamides / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology*; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3 / Q000819:agonists*; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017661:Receptors, Presynaptic / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects
D000700:Analgesics; D044482:Benzeneacetamides; D018491:Dopamine Agonists; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D017473:Receptors, Opioid, kappa; D017661:Receptors, Presynaptic; D019257:Quinpirole; C045444:U 69593