Modulation of rat brain cannabinoid receptors after chronic morphine treatment.
Intraperitoneal injection of delta9-THC (7.5 mg/kg) in rats made tolerant to morphine by s.c. implantation of morphine pellets had a much greater analgesic effect than in placebo pellet plus delta9-THC treatment. To investigate whether this was due to some change in cannabinoid receptor levels and/or expression induced by chronic morphine, we designed this autoradiographic binding study coupled with in situ hybridization on sagittal sections of the treated rat brains. Binding showed a significant increase in CB1 receptor density (15%) specifically in the caudate-putamen, in parallel with a significant enhancement of CB1 mRNA in the same area (20%). We suggest that morphine chronic treatment leads to a functional modulation between the opioid and cannabinoid systems at least for analgesia in a specific area, in this case the striatum.
Rubino
T
T
Institute of Pharmacology, Faculty of Sciences, University of Milan, Italy.
Tizzoni
L
L
Viganò
D
D
Massi
P
P
Parolaro
D
D
D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects; D013759:Dronabinol / Q000494:pharmacology*; D004361:Drug Tolerance; D017403:In Situ Hybridization; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000096:biosynthesis / Q000187:drug effects*
D000700:Analgesics; D000701:Analgesics, Opioid; D012333:RNA, Messenger; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D009020:Morphine; D013759:Dronabinol