Investigation of the role of alpha-2 adrenergic receptors on prepulse inhibition of acoustic startle reflex in rats

摘要

Objectives: Alpha-2 adrenergic receptors target several behavioral functions. These receptors may connect with the brain pathways mediating sensorimotor gating system that associate with psychoses, and the literature that investigate the relationship between alpha-2 receptors and sensorimotor gating system is very limited and some results are controversial. Thus, we aimed to investigate the role of alpha-2 receptors on prepulse inhibition (PPI) of acoustic startle reflex which is a measure of sensorimotor gating. Experimental Design: Adult male Wistar rats were subjects. PPI was measured as the per cent inhibition of the startle reflex produced by a startling pulse stimulus. The average PPI levels were used in the further analyses. Clonidine (0.03-1 mg/kg), an agonist of alpha-2 receptors, idazoxan (10 mg/kg), an antagonist alpha-2 receptors, and saline were injected to rats intraperitoneally. PPI was evaluated at two different startle intensity levels (78 and 86 dB, respectively). Principal Observations: Treatments produced some significant changes on PPI of startle reflex at all two levels of startle intensity. While clonidine (0.06, 0.25, 0.5, and 1 mg/kg) disrupted significantly PPI, idazoxan (10 mg/kg) did not produce any significant effect on PPI. However, pretreatment with idazoxan reversed significantly clonidine-induced disruption of PPI. Neither idazoxan (10 mg/kg) nor clonidine (1 mg/kg) produces any significant change on locomotor activity in naive rats. Conclusion: Because idazoxan and clonidine also act through imidazoline receptors, our results suggest that alpha-2 and/or imidazoline receptors are associated with PPI of acoustic startle reflex in rats. Stimulation of these receptors may cause sensorimotor gating disturbances.