[26]. Moreover, ML297 did not affect locomotor activity in the open-field test, and did not show significant reinforcing effects in the conditioned place preference test at the studied dose (30 mg/kg i.p.). This suggested that the anxiolytic effects were not related to reduced locomotion due to sedation, nor to a rewarding effect of ML297 [26]. Recently, Zou et al investigated the potential for ML297 to treat insomnia, under the hypothesis that direct GIRK activation would avoid side-effects associated with the use of GABAB receptor agonists [28]. In hypothalamic brain slices, ML297 (10 μM) produced long-lasting hyperpolarization and blocked spontaneous firing of action potentials in hypocretin neurons (Table 1). Systemic injection of ML297 (30 mg/kg i.p.) reduced wake activity and locomotion and increased non-rapid eye movement (NREM) sleep in mice, without inducing spike-wave discharges (an absence seizure activity) or memory impairment (Figure 3) [28].
