Early maternal deprivation and neonatal single administration with a cannabinoid agonist induce long-term sex-dependent psychoimmunoendocrine effects in adolescent rats.
Maternal deprivation [24h on postnatal day 9] might represent an animal model of schizophrenia and behavioural and neurochemical alterations observed in adulthood may be mediated by hippocampal impairments induced by abnormally increased glucocorticoids due to neonatal stress. We aimed to provide new data for psychoimmunoendocrine characterization of this animal model by evaluating its effects in adolescent rats of both genders. In previous studies we found that cannabinoid compounds counteracted the enhanced impulsivity of maternally deprived animals and that the cannabinoid receptor agonist WIN 55,212-2 showed neuroprotective properties in neonatal rats. So, we hypothesised that this compound could counteract at least some of the detrimental effects that we expected to find in maternally deprived animals. Accordingly, the drug was administered immediately after the maternal deprivation period. Maternally deprived males showed significantly decreased motor activity in the holeboard and the plus-maze. The cannabinoid agonist induced, exclusively in males, a significant anxiogenic-like effect, which was reversed by maternal deprivation. In the forced swimming test, both treatments independently induced depressive-like responses. Maternal deprivation reduced immunological function whereas the drug exerted tissue-dependent effects on the immune parameters analysed. Maternally deprived females showed reduced corticosterone levels whereas the cannabinoid agonist increased hormone concentration in all groups. In general, the results show detrimental effects of both treatments as well as intriguing interactions, notably in relation to emotional behaviour and certain immunological responses.
Llorente
Ricardo
R
Departamento de Fisiología (Fisiología Animal II), Facultad de Ciencias Biológicas, Universidad Complutense, Ciudad Universitaria, C/ Jose Antonio Novais, 2; 28040 Madrid, Spain.
Arranz
Lorena
L
Marco
Eva-María
EM
Moreno
Enrique
E
Puerto
Marta
M
Guaza
Carmen
C
De la Fuente
Mónica
M
Viveros
Maria-Paz
MP
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D048588:Benzoxazines / Q000008:administration & dosage*; D001835:Body Weight / Q000187:drug effects; D002186:Cannabinoids / Q000819:agonists*; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D007279:Injections, Subcutaneous; D008297:Male; D008426:Maternal Deprivation; D018782:Maze Learning / Q000187:drug effects; D009025:Morpholines / Q000008:administration & dosage*; D009281:Naphthalenes / Q000008:administration & dosage*; D015213:Neuroimmunomodulation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012741:Sexual Maturation / Q000187:drug effects*; D013550:Swimming; D013997:Time Factors
D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D003345:Corticosterone