Increasing CB2 Receptor Activity after Early Life Stress Prevents Depressive Behavior in Female Rats.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101596414 Publication Model: Electronic Cited Medium: Internet ISSN: 2218-273X (Electronic) Linking ISSN: 2218273X NLM ISO Abbreviation: Biomolecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, 2011-

Receptor, Cannabinoid, CB2*/metabolism ; Depression*/metabolism ; Maternal Deprivation* ; Stress, Psychological*/metabolism; Animals ; Female ; Rats ; Parvalbumins/metabolism ; Behavior, Animal ; Rats, Sprague-Dawley ; Cannabinoids/pharmacology

Early adversity, the loss of the inhibitory GABAergic interneuron parvalbumin, and elevated neuroinflammation are associated with depression. Individuals with a maltreatment history initiate medicinal cannabis use earlier in life than non-maltreated individuals, suggesting self-medication. Female rats underwent maternal separation (MS) between 2 and 20 days of age to model early adversity or served as colony controls. The prelimbic cortex and behavior were examined to determine whether MS alters the cannabinoid receptor 2 (CB2), which has anti-inflammatory properties. A reduction in the CB2-associated regulatory enzyme MARCH7 leading to increased NLRP3 was observed with Western immunoblots in MS females. Immunohistochemistry with stereology quantified numbers of parvalbumin-immunoreactive cells and CB2 at 25, 40, and 100 days of age, revealing that the CB2 receptor associated with PV neurons initially increases at P25 and subsequently decreases by P40 in MS animals, with no change in controls. Confocal and triple-label microscopy suggest colocalization of these CB2 receptors to microglia wrapped around the parvalbumin neuron. Depressive-like behavior in MS animals was elevated at P40 and reduced with the CB2 agonist HU-308 or a CB2-overexpressing lentivirus microinjected into the prelimbic cortex. These results suggest that increasing CB2 expression by P40 in the prelimbic cortex prevents depressive behavior in MS female rats.

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DA-R56 043991 United States DA NIDA NIH HHS; R21 DA041833-01 United States DA NIDA NIH HHS

Keywords: CB2; PV; adversity; depression; female; inflammation; microglia; stress

0 (Receptor, Cannabinoid, CB2)
0 (Parvalbumins)
8I5L034D55 (HU 308)
0 (Cannabinoids)
0 (Cnr2 protein, rat)

Date Created: 20240427 Date Completed: 20240427 Latest Revision: 20240528

20240528

PMC11047932

10.3390/biom14040464

38672480