Effects of the Phosphodiesterase 10A Inhibitor MR1916 on Alcohol Self-Administration and Striatal Gene Expression in Post-Chronic Intermittent Ethanol-Exposed Rats
| dc.contributor.author | Bertotto, Luísa B. | en |
| dc.contributor.author | Lampson-Stixrud, Dolly | en |
| dc.contributor.author | Sinha, Anushka | en |
| dc.contributor.author | Rohani, Nicki K. | en |
| dc.contributor.author | Myer, Isabella | en |
| dc.contributor.author | Zorrilla, Eric P. | en |
| dc.date.accessioned | 2024-02-23T15:17:14Z | en |
| dc.date.available | 2024-02-23T15:17:14Z | en |
| dc.date.issued | 2024-02-09 | en |
| dc.date.updated | 2024-02-23T15:03:17Z | en |
| dc.description.abstract | Alcohol use disorder (AUD) requires new neurobiological targets. Problematic drinking involves underactive indirect pathway medium spiny neurons (iMSNs) that subserve adaptive behavioral selection vs. overactive direct pathway MSNs (dMSNs) that promote drinking, with a shift from ventromedial to dorsolateral striatal (VMS, DLS) control of EtOH-related behavior. We hypothesized that inhibiting phosphodiesterase 10A (PDE10A), enriched in striatal MSNs, would reduce EtOH self-administration in rats with a history of chronic intermittent ethanol exposure. To test this, Wistar rats (<i>n</i> = 10/sex) with a history of chronic intermittent EtOH (CIE) vapor exposure received MR1916 (i.p., 0, 0.05, 0.1, 0.2, and 0.4 µmol/kg), a PDE10A inhibitor, before operant EtOH self-administration sessions. We determined whether MR1916 altered the expression of MSN markers (<i>Pde10a</i>, <i>Drd1</i>, <i>Drd2</i>, <i>Penk</i>, and <i>Tac1</i>) and immediate-early genes (IEG) (<i>Fos</i>, <i>Fosb</i>, Δ<i>Fosb</i>, and <i>Egr1</i>) in EtOH-naïve (<i>n</i> = 5–6/grp) and post-CIE (<i>n</i> = 6–8/grp) rats. MR1916 reduced the EtOH self-administration of high-drinking, post-CIE males, but increased it at a low, but not higher, doses, in females and low-drinking males. MR1916 increased <i>Egr1</i>, <i>Fos</i>, and <i>FosB</i> in the DLS, modulated by sex and alcohol history. MR1916 elicited dMSN vs. iMSN markers differently in ethanol-naïve vs. post-CIE rats. High-drinking, post-CIE males showed higher DLS <i>Drd1</i> and VMS IEG expression. Our results implicate a role and potential striatal bases of PDE10A inhibitors to influence post-dependent drinking. | en |
| dc.description.version | Published version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.citation | Bertotto, L.B.; Lampson-Stixrud, D.; Sinha, A.; Rohani, N.K.; Myer, I.; Zorrilla, E.P. Effects of the Phosphodiesterase 10A Inhibitor MR1916 on Alcohol Self-Administration and Striatal Gene Expression in Post-Chronic Intermittent Ethanol-Exposed Rats. Cells 2024, 13, 321. | en |
| dc.identifier.doi | https://doi.org/10.3390/cells13040321 | en |
| dc.identifier.uri | https://hdl.handle.net/10919/118123 | en |
| dc.language.iso | en | en |
| dc.publisher | MDPI | en |
| dc.rights | Creative Commons Attribution 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
| dc.subject | ethanol or alcohol intake | en |
| dc.subject | dorsal striatum or nucleus accumbens | en |
| dc.subject | alcohol use disorder | en |
| dc.subject | medium spiny neuron | en |
| dc.subject | immediate-early gene expression | en |
| dc.subject | PDE10A | en |
| dc.title | Effects of the Phosphodiesterase 10A Inhibitor MR1916 on Alcohol Self-Administration and Striatal Gene Expression in Post-Chronic Intermittent Ethanol-Exposed Rats | en |
| dc.title.serial | Cells | en |
| dc.type | Article - Refereed | en |
| dc.type.dcmitype | Text | en |