Hispidulin alleviated methamphetamine-induced hyperlocomotion by acting at α6 subunit-containing GABAA receptors in the cerebellum

Abstract

It is suggested that hispidulin alleviates MIH via acting as a PAM of cerebellar α6GABAARs, but not through COMT inhibition or affecting dopamine receptor responsiveness. Thus, selective α6GABAAR PAMs may have the potential to be a novel treatment for hyperdopaminergic disorders.

Cerebellar α6‐subunit‐containing GABAA receptors: a novel therapeutic target for disrupted prepulse inhibition in neuropsychiatric disorders

“…Bilateral i.cb. microinjection was performed as described previously (Liao et al ., ). Briefly, the mouse was, under anaesthesia, implanted with two 24‐gauge stainless‐steel guide cannulas, respectively, directed towards the right and left lateral cerebella (−6.4 mm caudal, ±1.5 mm lateral and −1.0 mm ventral from bregma) (Paxinos and Franklin, ).…”

“…Hispidulin, Ro15‐4513, loreclezole, diazepam and furosemide, when administered by i.cb. microinjection, were dissolved in DMSO as reported previously (Liao et al ., ). All drugs were administered 10 min before the test session unless stated otherwise.…”

“…It is noteworthy that hispidulin is a PAM of α 6 ‐subunit‐containing GABA A receptors (α 6 GABA A receptors) that are mainly expressed in the granule cells of the cerebellum (Gutierrez et al ., ; Pirker et al ., ). Among 92 neurotransmitter receptors, enzymes and transporters, we found that hispidulin displayed micromolar affinity only at GABA A receptors and COMT (Liao et al ., ). Further, hispidulin alleviated MIH in mice by acting as a PAM at cerebellar α 6 GABA A receptors, but not as a COMT inhibitor, at doses without benzodiazepine‐like effects, such as sedation, anxiolysis and motor impairment (Liao et al ., ).…”

“…Among 92 neurotransmitter receptors, enzymes and transporters, we found that hispidulin displayed micromolar affinity only at GABA A receptors and COMT (Liao et al ., ). Further, hispidulin alleviated MIH in mice by acting as a PAM at cerebellar α 6 GABA A receptors, but not as a COMT inhibitor, at doses without benzodiazepine‐like effects, such as sedation, anxiolysis and motor impairment (Liao et al ., ).…”

Fast analysis of benzodiazepines using argon direct analysis in real time mass spectrometry on‐line coupled with a thermal‐assisted gasification injector

“…Benzodiazepines as pharmaceuticals used to treat mental conditions are poisonous when they are overdosed. [1][2][3] The abuse of benzodiazepines has become a serious social problem which has also led to a number of crimes. At present, the commonly used approaches to analyze these drugs are high-performance liquid chromatography and thin-layer chromatography.…”