Antinociceptive, behavioural and neuroendocrine effects of CP 55,940 in young rats.
The peripubertal period appears to be critical in relation to the abuse of cannabinoids and opioids in humans. However there is little information about the acute effects of cannabinoids and their interactions with opioids in young experimental animals. We have studied the effects of the cannabinoid agonist CP 55,940 (0.1, 0.2, 0.4 and 0.6 mg/kg) on the nociceptive responses (tail immersion test) and holeboard activity of 40-day-old rats, and the involvement of the CB(1) receptor (antagonism by SR 141716A, 3 mg/kg). The implication of the opioid system was evaluated using the opioid antagonist naloxone (1 mg/kg) and a combined treatment with subeffective doses of CP 55,940 (0.1 mg/kg) and morphine (1 mg/kg). The effects of CP 55,940 on the serum corticosterone levels (radioimmunoassay) and on the dopamine and DOPAC contents of discrete brain regions (high-performance liquid chromatography) were also assessed. The antinociceptive effect of CP 55,940 was of a similar magnitude at all the doses used. The results show the involvement of the CB(1) receptor. The cannabinoid agonist significantly depressed the holeboard activity in a dose-dependent manner. The results indicate that the CB(1) receptor is involved in the effects on motor activity but not in the effects on the exploratory activity. The behavioural effects of CP 55,940 were modulated by morphine. The cannabinoid agonist (0.6 mg/kg) induced a CB(1)-mediated increase in the serum corticosterone levels, but no effect on the dopaminergic systems of either the striatum or the limbic forebrain was found.
Romero
Eva M
EM
Departamento de Biología Animal II, Facultad de Biología, Universidad Complutense, 28040 Madrid, Spain.
Fernández
Beatriz
B
Sagredo
Onintza
O
Gomez
Nuria
N
Urigüen
Leyre
L
Guaza
Carmen
C
De Miguel
Rosario
R
Ramos
Jose Antonio
JA
Viveros
M Paz
MP
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D002186:Cannabinoids / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D003511:Cyclohexanols / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D006120:Grooming / Q000187:drug effects / Q000502:physiology; D008297:Male; D002189:Marijuana Abuse / Q000378:metabolism* / Q000503:physiopathology; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077285:Rimonabant; D012727:Sex Characteristics
D000700:Analgesics; D002186:Cannabinoids; D003511:Cyclohexanols; D009292:Narcotic Antagonists; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D009270:Naloxone; D009020:Morphine; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D000077285:Rimonabant; D004298:Dopamine; D003345:Corticosterone