Titre du document / Document title

Milk intake and survival in newborn cannabinoid CB₁ receptor knockout mice: evidence for a CB₃ receptor

Auteur(s) / Author(s)

FRIDE Ester ^{(1 2)} ; FOOX Anat ⁽¹⁾ ; ROSENBERG Elana ⁽³⁾ ; FAIGENBOIM Moran ⁽¹⁾ ; COHEN Vickey ⁽¹⁾ ; BARDA Lena ⁽¹⁾ ; BLAU Hannah ⁽⁴⁾ ; MECHOULAM Raphael ⁽³⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Behavioral Sciences, College of Judea and Samaria, Ariel 44837, ISRAEL
⁽²⁾ Department of Health Sciences, College of Judea and Samaria, Ariel 44837, ISRAEL
⁽³⁾ Department of Medicinal Chemistry and Natural Products, Medical Faculty, Hebrew University of Jerusalem, ISRAEL
⁽⁴⁾ Pulmonary Unit, Schneider Children's Medical Center of Israel, Petach Tikya, ISRAEL

Résumé / Abstract

Cannabinoids, whether plant-derived, synthetic or endogenous, have been shown to stimulate appetite in the adult organism. We have reported previously that cannabinoid receptors play a critical role during the early suckling period: The selective cannabinoid CB₁ receptor antagonist N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141617A) permanently prevented milk ingestion in a dose-dependent manner, when administered to (Sabra, albino) mouse pups, within 1 day of birth. As a consequence, these pups died within the first week of life. We now generalize this finding to a different strain of mice (C57BL/6). Further, we show that cannabinoid CB₁ receptor blockade (20 mg/kg SR141716A) must occur within 24 h after birth as injection of SR141716A into 2-or 5-day-old pups had a much smaller effect or no effect at all, respectively. Cannabinoid CB₁ receptor knockout mice did not ingest milk on the first day of life, similarly to SR141716A-treated normal pups, as measured by the appearance of milkbands. However, the knockout pups started to display milkbands from day 2 of life. Survival rates of cannabinoid CB₁ receptor knockout mice were affected significantly, but to a lesser extent than normal pups, by the administration of SR141716A. Daily administration of the endocannabinoid 2-arachidonoyl glycerol, or the synthetic agonists (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naph-thalenylmethanone (WIN55,212-2, 5 mg/kg) or (-)-cis-3-[2-Hydroxy4-(1,1-dimethylheptyl) phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol (CP55,940, 5 or 20 mg/kg) did not promote survival or weight gain in CB^-/-₁ pups. Our data support previous evidence for a critical role of cannabinoid CB₁ receptors for the initiation of suckling. Further, the present observations support the existence of an unknown cannabinoid receptor, with partial control over milk ingestion in newboms. Our data also suggest that the CB^-/-₁ neonates possess a compensatory mechanism which helps them overcome the lack of cannabinoid CB₁ receptors.

Revue / Journal Title

European journal of pharmacology   ISSN 0014-2999   CODEN EJPHAZ 

Source / Source

2003, vol. 461, n^o1, pp. 27-34 [8 page(s) (article)] (38 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1967) (Revue)

Mots-clés anglais / English Keywords

Vertebrata ; Mammalia ; Rodentia ; Central nervous system ; Brain (vertebrata) ; Neuromodulation ; Mechanism of action ; Breast milk ; Regulation(control) ; Suckling ; Newborn animal ; Suckling animal ; Appetite stimulant ; Molecular form ; Cannabinoid receptor ; Mouse ; Animal ; CB1 cannabinoid receptor ;

Mots-clés français / French Keywords

Vertebrata ; Mammalia ; Rodentia ; Récepteur cannabinoïde CB3 ; Système nerveux central ; Encéphale ; Neuromodulation ; Mécanisme action ; Lait maternel ; Régulation ; Tétée ; Animal nouveau né ; Animal allaité ; Orexigène ; Forme moléculaire ; Récepteur cannabinoïde ; Souris ; Animal ; Récepteur cannabinoïde CB1 ;

Mots-clés espagnols / Spanish Keywords

Vertebrata ; Mammalia ; Rodentia ; Sistema nervioso central ; Encéfalo ; Neuromodulación ; Mecanismo acción ; Leche materna ; Regulación ; Mamada ; Animal recién nacido ; Animal lactante ; Orexígeno ; Forma molecular ; Receptor canabinoide ; Ratón ; Animal ; Receptor canabinoide CB1 ;

Mots-clés d'auteur / Author Keywords

keyworkds: 2-Arachidonoyl glycerol ; Endocannabinoid ; Cannabinoid receptor ; Milk suckling ; SR141716A ; Cannabidiol ;

Localisation / Location

INIST-CNRS, Cote INIST : 13322, 35400010750462.0040