Cannabinoid-induced Fos expression within A10 dopaminergic neurons.
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.
Patel
Sachin
S
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Hillard
Cecilia J
CJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D003511:Cyclohexanols / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D007150:Immunohistochemistry; D008032:Limbic System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008125:Locus Coeruleus / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002186:Cannabinoids; D003511:Cyclohexanols; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D003000:Clonidine; D004298:Dopamine; D009638:Norepinephrine; D011224:Prazosin