TY  - JOUR
PY  - 2001//
TI  - Evaluation of the alpha2C-adrenoceptor as a neuropsychiatric drug target studies in transgenic mouse models
JO  - Life Sciences
A1  - Scheinin, M.
A1  - Sallinen, J.
A1  - Haapalinna, A.
SP  - 2277
EP  - 2285
VL  - 68
IS  - 19-20
N2  - The functional characterization of the three distinct alpha2-adrenoceptor (Q2-AR) subtypes was for long hampered by the inavailability of subtype-selective pharmacological probes. Recent studies with gene-targeted mice have revealed that the alpha2A-AR has a major role in the mediation of many prominent effects of subtype non-selective alpha2-AR agonists, i.e. sedation, analgesia, hypothermia, sympatho-inhibition, and reduction of blood pressure. We have now employed several neuropsychopharmacological test models to investigate the effects mediated by the alpha2C-AR subtype and this receptor's potential as a CNS drug target. The studies employed two genetically engineered mouse strains, having either a targeted inactivation of the alpha2C-AR gene (alpha2C-KO) or over-expressing the alpha2C-AR (alpha2C-OE). Lack of alpha2C-AR expression was associated with increased amphetamine-induced locomotor activity, startle reactivity, aggression, and activity in the forced swimming test; prepulse inhibition of the startle reflex was attenuated. Opposite changes were observed in the alpha2C-OE mice. The results suggest that the alpha2C-AR subtype has a distinct inhibitory role in the processing of sensory information and in the control of motor and emotion-related activities in the CNS. It is therefore possible that alpha2C-AR-selective drugs may have therapeutic value in the treatment of various neuropsychiatric disorders.<p /> <p>Language: en</p>
LA  - en
SN  - 0024-3205
UR  - http://dx.doi.org/
ID  - ref1
ER  -