Faculty Collaboration Database

Cannabinoid-induced Fos expression within A10 dopaminergic neurons. Brain Res 2003 Feb 14;963(1-2):15-25

Date

02/01/2003

Pubmed ID

12560108

DOI

10.1016/s0006-8993(02)03797-6

Scopus ID

2-s2.0-0037435933 (requires institutional sign-in at Scopus site)   57 Citations

Abstract

Mesocorticolimbic dopaminergic systems subserve cognitive processes, motivated behavior, the central stress response, and the reinforcing properties of drugs of abuse. Hyperdopaminergic states have been suggested to contribute to the psychotropic effects of the cannabinoids; however, the mechanisms by which cannabinoids activate mesocorticolimbic dopaminergic systems are not well understood. We have examined the role of noradrenergic neurotransmission in the mediation of cannabinoid-induced activation of A10 dopaminergic neurons using Fos as a marker of neuronal activation in mice. Administration of the CB(1) receptor agonist CP55940 differentially increased the number of Fos-like immunoreactive (Fos-li) A10 dopaminergic cells within three anatomically distinct regions (parabrachial pigmented, paranigral, and caudal linear nuclei) compared to vehicle-treated mice. Similar results were obtained using the CB(1) receptor agonist Win 55212-2; and pretreatment with the CB(1) receptor antagonist SR141716 significantly inhibited CP55940-induced Fos expression. Pretreatment with the alpha(1)-adrenergic receptor antagonist, prazosin, and the alpha(2)-adrenergic receptor agonist, clonidine, reduced the number of Fos-li dopaminergic neurons induced by CP55940 in a subregion-specific manner. CP55940 and Win 55212-2 increased the number of Fos-li neurons within the locus coeruleus. Finally, CB(1) receptor immunoreactivity was detected on fibers within the CL but not in either PBP or PN. Our data demonstrate that cannabinoids induce Fos expression within A10 dopaminergic neurons in a heterogeneous anatomical pattern, and suggest that enhanced noradrenergic neurotransmission contributes to cannabinoid-induced activation of A10 dopaminergic neurons in vivo.

Author List

Patel S, Hillard CJ

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenergic alpha-Agonists
Adrenergic alpha-Antagonists
Animals
Cannabinoids
Cerebral Cortex
Clonidine
Cyclohexanols
Dopamine
Gene Expression Regulation
Genes, fos
Immunohistochemistry
Limbic System
Locus Coeruleus
Male
Mice
Mice, Inbred ICR
Neurons
Norepinephrine
Prazosin
Receptors, Cannabinoid
Receptors, Drug
Synaptic Transmission