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.
Introini-Collison
I B
IB
Center for the Neurobiology of Learning and Memory, University of California, Irvine 92717-3800.
Castellano
C
C
McGaugh
J L
JL
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001640:Bicuculline / Q000494:pharmacology; D002976:Clenbuterol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D005239:Fear / Q000187:drug effects / Q000502:physiology; D008297:Male; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009638:Norepinephrine / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D011433:Propranolol; D009638:Norepinephrine; D002976:Clenbuterol; D001640:Bicuculline