| First Author | Sallinen J | Year | 1998 |
| Journal | Neuroscience | Volume | 86 |
| Issue | 3 | Pages | 959-65 |
| PubMed ID | 9692731 | Mgi Jnum | J:49002 |
| Mgi Id | MGI:1276305 | Doi | 10.1016/s0306-4522(98)00100-6 |
| Citation | Sallinen J, et al. (1998) D-amphetamine and L-5-hydroxytryptophan-induced behaviours in mice with genetically-altered expression of the alpha2C-adrenergic receptor subtype. Neuroscience 86(3):959-65 |
| abstractText | Three human and mouse genes encoding alpha(2)-adrenoceptor subtypes (alpha(2A), alpha(2B), and alpha(2C)) have been cloned. The alpha(2C)-adrenoceptor is the most abundant alpha(2)-adrenoceptor subtype in the striatum and modulates metabolism of both dopamine and serotonin. To investigate the possible involvement of the alpha(2C)- adrenoceplor subtype in behaviours regulated by dopamine and serotonin, two strains of genetically-engineered mice were examined. One had a targeted inactivation of the alpha(2C)-adrenoceptor gene, and the other had tissue- specific over-expression of alpha(2C)-adrenoceptors. The locomotor activity of the mice was evaluated after stimulation with D-amphetamine, and the behavioural serotonin syndrome and head twitches were investigated after L-5-hydroxytryptophan treatment. In addition, the effects of D-amphetamine and L-5-hydroxytryptophan were studied after pretreatment with dexmedetomidine, a subtype- nonselective alpha(2)-adrenoceptor agonist. The lack of alpha(2C)-adrenoceptor expression increased and the over- expression of alpha(2C)-adrenoceptors decreased the response to D-amphetamine stimulation. The effect of alpha(2C)-adrenoceptor gene inactivation was more prominent in D-amphelamine-treated males than in females. Dexmedetomidine inhibited D-amphetamine-induced hyperlocomotion and the L-5-hydroxytryptophan-induced serotonin syndrome, but the inhibition was attenuated in mice lacking alpha(2C)-adrenoceptors. However, the head twitches induced by L-5-hpdroxytryptophan were effectively inhibited by dexmedetomidine in all studied mice, which suggests that alpha(2A)-adrenoceptors mediate the inhibition of the head twitch response. The results lend further support to the proposed existence of functionally distinct alpha(2)-adrenoceptor subtypes that can serve as new and specific therapeutic targets in various neuropsychiatric diseases. (C) 1998 IBRO. Published by Elsevier Science Ltd. |
