Effects of salvinorin A on locomotor sensitization to D2/D3 dopamine agonist quinpirole.
Locomotor sensitization induced by the dopamine agonist quinpirole can be potentiated by co-treatment with the synthetic kappa opioid agonist U69593. The identification of salvinorin A, an active component of the psychotropic sage Salvia divinorum, as a structurally different agonist of kappa-opioid receptors raised the question of whether this compound would similarly potentiate sensitization to quinpirole. Rats were co-treated with 0.5 mg/kg quinpirole and either salvinorin A (0.04, 0.4 or 2.0 mg/kg) or U69593 (0.3 mg/kg). Control groups were co-treated with vehicle and saline, vehicle and quinpirole (0.5 mg/kg), or saline and salvinorin A (0.4 mg/kg). Rats were injected biweekly for a total of 10 injections and locomotor activity measured after each treatment. Results showed that the highest dose of salvinorin A potentiated sensitization to quinpirole as did U69593, the middle salvinorin A dose had no effect on quinpirole sensitization, and the lowest dose of salvinorin A attenuated sensitization to quinpirole. These findings indicate that structural differences between salvinorin A and U69593 do not affect the potentiation of quinpirole sensitization. Moreover, the opposite effects of high and low salvinorin A doses suggest that salvinorin A can produce bidirectional modulation of sensitization to dopamine agonists.
Beerepoot
Pieter
P
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada.
Lam
Vincent
V
Luu
Alice
A
Tsoi
Bernice
B
Siebert
Daniel
D
Szechtman
Henry
H
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D045785:Diterpenes, Clerodane / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004351:Drug Resistance / Q000187:drug effects / Q000502:physiology; D004357:Drug Synergism; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D011759:Pyrrolidines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000819:agonists*; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000700:Analgesics; D044482:Benzeneacetamides; D045785:Diterpenes, Clerodane; D015259:Dopamine Agents; D018491:Dopamine Agonists; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D017473:Receptors, Opioid, kappa; D019257:Quinpirole; C045444:U 69593; C090499:salvinorin A; D004298:Dopamine