| First Author | Lazenka MF | Year | 2015 |
| Journal | J Pharmacol Exp Ther | Volume | 354 |
| Issue | 3 | Pages | 316-27 |
| PubMed ID | 26099530 | Mgi Jnum | J:335465 |
| Mgi Id | MGI:6869012 | Doi | 10.1124/jpet.115.224428 |
| Citation | Lazenka MF, et al. (2015) Role of Dopamine Type 1 Receptors and Dopamine- and cAMP-Regulated Phosphoprotein Mr 32 kDa in Delta9-Tetrahydrocannabinol-Mediated Induction of DeltaFosB in the Mouse Forebrain. J Pharmacol Exp Ther 354(3):316-27 |
| abstractText | Delta(9)-Tetrahydrocannabinol (THC), the main psychoactive component of marijuana, produces motor and motivational effects via interactions with the dopaminergic system in the caudate-putamen and nucleus accumbens. However, the molecular events that underlie these interactions after THC treatment are not well understood. Our study shows that pretreatment with dopamine D1 receptor (D1R) antagonists before repeated administration of THC attenuated induction of Delta FBJ murine osteosarcoma viral oncogene homolog B (DeltaFosB) in the nucleus accumbens, caudate-putamen, amygdala, and prefrontal cortex. Anatomical studies showed that repeated THC administration induced DeltaFosB in D1R-containing striatal neurons. Dopamine signaling in the striatum involves phosphorylation-specific effects of the dopamine- and cAMP-regulated phosphoprotein Mr 32 kDa (DARPP-32), which regulates protein kinase A signaling. Genetic deletion of DARPP-32 attenuated DeltaFosB expression measured after acute, but not repeated, THC administration in both the caudate-putamen and nucleus accumbens. THC was then acutely or repeatedly administered to wild-type (WT) and DARPP-32 knockout (KO) mice, and in vivo responses were measured. DARPP-32 KO mice exhibited enhanced acute THC-mediated hypolocomotion and developed greater tolerance to this response relative to the WT mice. Agonist-stimulated guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding showed that cannabinoid-stimulated G-protein activity did not differ between DARPP-32 KO and WT mice treated with vehicle or repeated THC. These results indicate that D1Rs play a major role in THC-mediated DeltaFosB induction in the forebrain, whereas the role of DARPP-32 in THC-mediated DeltaFosB induction and modulation of motor activity appears to be more complex. |
