Behavioural evidence for GABAergic activity of the benzodiazepine flurazepam

Following reports that unilateral intranigral injections of putative GABAergic drugs induce contralateral rotational behaviour in rats, the effects of similar injections of the benzodiazepine flurazepam have been studied. Flurazepam mimicked the effects of the GABA agonist muscimol and the GABA analogue baclofen by inducing a dose-related contralateral rotation. This response was anatomically associated with the GABA-rich zona reticulata of the substantia nigra and was attenuated by the GABA antagonist picrotoxin but not by the dopamine antagonist haloperidol or by destruction of the ipsilateral nigrostriatal dopamine pathway with 6-hydroxydopamine. These results suggest that in this behavioural model flurazepam may show GABAergic activity by indirectly enhancing GABA transmission at synapses with receptors located on nigral non-dopaminergic neurons controlling postural asymmetry.