Interaction of GABAergic and beta-noradrenergic drugs in the regulation of memory storage

These experiments examined the interaction of drugs affecting noradrenergic and GABAergic systems, administered post-training, in influencing retention of an inhibitory avoidance response. Male CD1 mice (23-28 g) were trained in an inhibitory avoidance task, given immediate post-training ip injections of saline or GABAergic and adrenergic drugs administered either alone or concurrently. Retention was tested 48 h later. In agreement with extensive previous evidence, the GABAergic antagonist bicuculline (0.3, 1.0, or 3.0 mg/kg) produced dose-dependent (inverted-U) enhancement of retention and the GABAergic agonist muscimol (1.0 mg/kg) impaired retention. The retention-enhancing effects of bicuculline were blocked by concurrent administration of the beta-nor-adrenoceptor antagonist propranolol (2.0 mg/kg). Also in agreement with previous evidence, the beta-adrenoceptor agonist clenbuterol (0.030, 0.100, or 0.300 mg/kg, ip) produced dose-dependent (inverted-U) enhancement of retention. Clenbuterol also blocked the retention-impairing effects of muscimol (1.0 mg/kg). In addition, propranolol (2.0 mg/kg) potentiated the retention impairing effects of muscimol (1.0 or 3.0 mg/kg, ip). These findings support the view that GABAergic systems modulate memory through an interaction with beta-noradrenergic mechanisms.