| First Author | Chen YW | Year | 2014 |
| Journal | Schizophr Bull | Volume | 40 |
| Issue | 2 | Pages | 388-98 |
| PubMed ID | 23474853 | Mgi Jnum | J:311783 |
| Mgi Id | MGI:6780465 | Doi | 10.1093/schbul/sbt031 |
| Citation | Chen YW, et al. (2014) A sex- and region-specific role of Akt1 in the modulation of methamphetamine-induced hyperlocomotion and striatal neuronal activity: implications in schizophrenia and methamphetamine-induced psychosis. Schizophr Bull 40(2):388-98 |
| abstractText | AKT1 (also known as protein kinase B, alpha), a serine/threonine kinase of AKT family, has been implicated in both schizophrenia and methamphetamine (Meth) use disorders. AKT1 or its protein also has epistatic effects on the regulation of dopamine-dependent behaviors or drug effects, especially in the striatum. The aim of this study is to investigate the sex-specific role of Akt1 in the regulation of Meth-induced behavioral sensitization and the alterations of striatal neurons using Akt1(-/-) mice and wild-type littermates as a model. A series of 4 Experiments were conducted. Meth-induced hyperlocomotion and Meth-related alterations of brain activity were measured. The neural properties of striatal medium spiny neurons (MSNs) were also characterized. Further, 17beta-estradiol was applied to examine its protective effect in Meth-sensitized male mice. Our findings indicate that (1) Akt1(-/-) males were less sensitive to Meth-induced hyperlocomotion during Meth challenge compared with wild-type controls and Akt1(-/-) females, (2) further sex differences were revealed by coinjection of Meth with raclopride but not SCH23390 in Meth-sensitized Akt1(-/-) males, (3) Meth-induced alterations of striatal activity were confirmed in Akt1(-/-) males using microPET scan with (18)F-flurodeoxyglucose, (4) Akt1 deficiency had a significant impact on the electrophysiological and neuromorphological properties of striatal MSNs in male mice, and (5) subchronic injections of 17beta-estradiol prevented the reduction of Meth-induced hyperactivity in Meth-sensitized Akt1(-/-) male mice. This study highlights a sex- and region-specific effect of Akt1 in the regulation of dopamine-dependent behaviors and implies the importance of AKT1 in the modulation of sex differences in Meth sensitivity and schizophrenia. |
