Activation of mu opioid receptors in the nucleus raphe dorsalis blocks apomorphine-induced aggression in rats: serotonin appears not to be involved.
The role of mu opioid receptors in the nucleus raphe dorsalis (DR) in the control of apomorphine-induced aggression was studied in rats. Administration in the DR of a selective mu opioid receptor agonist, (D-Ala2,N-Me-Phe4,Gly5-ol)-enkephalin (DAGO), in doses ranging from 0.01 to 1 microgram/0.5 microliter, dose-dependently reduced aggression caused by apomorphine 20 mg/kg intraperitoneally. 0.01 microgram DAGO significantly reduced the time spent by the animals in aggressive posture and 0.1 and 1 microgram markedly reduced both aggressive postures and attacks. 5 micrograms (in 0.5 microliter) naloxone in the DR completely antagonized the anti-aggressive effect of DAGO (0.1 microgram/0.5 microliter) injected in the same area. 0.1 and 1 microgram but not 0.01 microgram DAGO significantly increased serotonin (5-HT) metabolism in the striatum, a terminal area almost exclusively innervated by DR, indicating that the activity of 5-HT cells in the DR was modified by DAGO. In animals given 6 micrograms/3 microliters 5,7-dihydroxytryptamine in the DR 11 days before, in which striatal 5-HT levels were markedly depleted, no significant changes were found in the time spent by the apomorphine-treated animals in aggressive postures, numbers of attacks or anti-aggressive effect of 0.1 and 1 microgram DAGO administered in the DR. The study shows for the first time that activation of mu opioid receptors in the DR has a powerful anti-aggressive effect in one model of experimental aggression by a mechanism apparently not involving changes in the activity of 5-HT cells in this area.
Giraud
O
O
Istituto di Ricerche Farmacologiche M. Negri, Milan, Italy.
Cervo
L
L
Grignaschi
G
G
Samanin
R
R
D000374:Aggression / Q000187:drug effects*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000494:pharmacology / Q000502:physiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D008297:Male; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu; D012701:Serotonin / Q000502:physiology*
D004723:Endorphins; D004745:Enkephalins; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D012701:Serotonin; D001058:Apomorphine