title: Enkephalin levels and the number of neuropeptide Y-containing interneurons in the hippocampus are decreased in female cannabinoid-receptor 1 knock-out mice.
abstract: Drug addiction requires learning and memory processes that are facilitated by activation of cannabinoid-1 (CB1) and opioid receptors in the hippocampus. This involves activity-dependent synaptic plasticity that is partially regulated by endogenous opioid (enkephalin and dynorphin) and non-opioid peptides, specifically cholecystokinin, parvalbumin and neuropeptide Y, the neuropeptides present in inhibitory interneurons that co-express CB1 or selective opioid receptors. We tested the hypothesis that CB1 receptor expression is a determinant of the availability of one or more of these peptide modulators in the hippocampus. This was achieved by quantitatively analyzing the immunoperoxidase labeling for each of these neuropeptide in the dorsal hippocampus of female wild-type (CB1+/+) and cannabinoid receptor 1 knockout (CB1-/-) C57/BL6 mice. The levels of Leu(5)-enkephalin-immunoreactivity were significantly reduced in the hilus of the dentate gyrus and in stratum lucidum of CA3 in CB1-/- mice. Moreover, the numbers of neuropeptide Y-immunoreactive interneurons in the dentate hilus were significantly lower in the CB1-/- compared to wild-type mice. However, CB1+/+ and CB1-/- mice did not significantly differ in expression levels of either dynorphin or cholecystokinin, and showed no differences in numbers of parvalbumin-containing interneurons. These findings suggest that the cannabinoid and opioid systems have a nuanced, regulatory relationship that could affect the balance of excitation and inhibition in the hippocampus and thus processes such as learning that rely on this balance.
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, United States. Electronic address: sarogers9@gmail.com.
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Rogers
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, United States; Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10021, United States.
authors.forename: Tracey A Van
authors.initials: TA
authors.lastname: Kempen
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, United States; Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10021, United States.
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Pickel
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, United States; Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10021, United States; Harold and Margaret Milliken Hatch Laboratory of Endocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, United States. Electronic address: tmilner@med.cornell.edu.
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Milner
mesh_terms: D000818:Animals; D002452:Cell Count; D002766:Cholecystokinin / Q000378:metabolism; D004399:Dynorphins / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*
chemical_list: D009478:Neuropeptide Y; D043884:Receptor, Cannabinoid, CB1; D004743:Enkephalin, Leucine; D004399:Dynorphins; D002766:Cholecystokinin
keywords: Cannabinoid; Female mice; Hippocampus; Neuropeptide Y; Opioid; Parvalbumin