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Dysregulation of the endogenous cannabinoid system in adult rats prenatally treated with the cannabinoid agonist WIN 55,212-2.
Eur J Pharmacol. 2007 Nov 14; 573(1-3):11-9.EJ

Abstract

Cannabis is widely abused by women at reproductive age and during pregnancy. Animal studies showed a particular vulnerability of the developing brain to prenatal chronic cannabinoid administration. We determined whether prenatal exposure to WIN 55,212-2, a potent cannabinoid receptor agonist, affected (1) density, affinity and/or function of cannabinoid CB(1) receptors, (2) endogenous levels of the endocannabinoid anandamide, (3) activities of the major anandamide synthesising and hydrolysing enzymes, N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH), respectively, in brain areas of adult male offspring rats. Furthermore, the effect of prenatal WIN 55,212-2 on spontaneous motility was analyzed. Pregnant rats were treated daily with WIN 55,212-2 (0.5 mg/kg, gestation day 5-20) or vehicle. [(3)H]CP 55,940 and WIN 55,212-2-stimulated [(35)S] GTPgammaS binding were carried out in cerebellum, cerebral cortex, hippocampus, striatum and limbic areas of male adult offspring. Levels of anandamide, FAAH and NAPE-PLD activity were also determined. EC(50) values for WIN 55,212-2-stimulated [(35)S]GTPgammaS binding were significantly different in hippocampus (-26%) and striatum (+27%) in WIN 55,212-2-treated rats. Cannabinoid CB(1) receptor density and affinity were not affected in any analyzed region. In the striatum, increased anandamide levels were associated with reduced FAAH and enhanced NAPE-PLD activities. Opposite changes in anandamide levels and enzymatic activities were detected in limbic areas of WIN 55,212-2-treated rats. Ambulatory activity between WIN 55,212-2- and vehicle-treated adult offspring did not vary. Our results show that prenatal exposure to cannabinoid agonist induces a long-term alteration of endocannabinoid system in brain areas involved in learning-memory, motor activity and emotional behavior.

Authors+Show Affiliations

Bernard B. Brodie Department of Neuroscience, University of Cagliari, 09042 Monserrato, Italy. castelli@unica.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17644084

Citation

Castelli, M Paola, et al. "Dysregulation of the Endogenous Cannabinoid System in Adult Rats Prenatally Treated With the Cannabinoid Agonist WIN 55,212-2." European Journal of Pharmacology, vol. 573, no. 1-3, 2007, pp. 11-9.
Castelli MP, Paola Piras A, D'Agostino A, et al. Dysregulation of the endogenous cannabinoid system in adult rats prenatally treated with the cannabinoid agonist WIN 55,212-2. Eur J Pharmacol. 2007;573(1-3):11-9.
Castelli, M. P., Paola Piras, A., D'Agostino, A., Pibiri, F., Perra, S., Gessa, G. L., Maccarrone, M., & Pistis, M. (2007). Dysregulation of the endogenous cannabinoid system in adult rats prenatally treated with the cannabinoid agonist WIN 55,212-2. European Journal of Pharmacology, 573(1-3), 11-9.
Castelli MP, et al. Dysregulation of the Endogenous Cannabinoid System in Adult Rats Prenatally Treated With the Cannabinoid Agonist WIN 55,212-2. Eur J Pharmacol. 2007 Nov 14;573(1-3):11-9. PubMed PMID: 17644084.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dysregulation of the endogenous cannabinoid system in adult rats prenatally treated with the cannabinoid agonist WIN 55,212-2. AU - Castelli,M Paola, AU - Paola Piras,A, AU - D'Agostino,Antonella, AU - Pibiri,Fabio, AU - Perra,Simona, AU - Gessa,Gian Luigi, AU - Maccarrone,Mauro, AU - Pistis,Marco, Y1 - 2007/07/04/ PY - 2007/02/13/received PY - 2007/06/21/revised PY - 2007/06/26/accepted PY - 2007/7/24/pubmed PY - 2008/3/14/medline PY - 2007/7/24/entrez SP - 11 EP - 9 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 573 IS - 1-3 N2 - Cannabis is widely abused by women at reproductive age and during pregnancy. Animal studies showed a particular vulnerability of the developing brain to prenatal chronic cannabinoid administration. We determined whether prenatal exposure to WIN 55,212-2, a potent cannabinoid receptor agonist, affected (1) density, affinity and/or function of cannabinoid CB(1) receptors, (2) endogenous levels of the endocannabinoid anandamide, (3) activities of the major anandamide synthesising and hydrolysing enzymes, N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH), respectively, in brain areas of adult male offspring rats. Furthermore, the effect of prenatal WIN 55,212-2 on spontaneous motility was analyzed. Pregnant rats were treated daily with WIN 55,212-2 (0.5 mg/kg, gestation day 5-20) or vehicle. [(3)H]CP 55,940 and WIN 55,212-2-stimulated [(35)S] GTPgammaS binding were carried out in cerebellum, cerebral cortex, hippocampus, striatum and limbic areas of male adult offspring. Levels of anandamide, FAAH and NAPE-PLD activity were also determined. EC(50) values for WIN 55,212-2-stimulated [(35)S]GTPgammaS binding were significantly different in hippocampus (-26%) and striatum (+27%) in WIN 55,212-2-treated rats. Cannabinoid CB(1) receptor density and affinity were not affected in any analyzed region. In the striatum, increased anandamide levels were associated with reduced FAAH and enhanced NAPE-PLD activities. Opposite changes in anandamide levels and enzymatic activities were detected in limbic areas of WIN 55,212-2-treated rats. Ambulatory activity between WIN 55,212-2- and vehicle-treated adult offspring did not vary. Our results show that prenatal exposure to cannabinoid agonist induces a long-term alteration of endocannabinoid system in brain areas involved in learning-memory, motor activity and emotional behavior. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17644084/Dysregulation_of_the_endogenous_cannabinoid_system_in_adult_rats_prenatally_treated_with_the_cannabinoid_agonist_WIN_55212_2_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00763-7 DB - PRIME DP - Unbound Medicine ER -