Enhancement of extinction memory consolidation: the role of the noradrenergic and GABAergic systems within the basolateral amygdala.
Evidence from previous studies indicates that the noradrenergic and GABAergic influences within the basolateral amygdala (BLA) modulate the consolidation of memory for fear conditioning. The present experiments investigated whether the same modulatory influences are involved in regulating the extinction of fear-based learning. To investigate this issue, male Sprague Dawley rats implanted with unilateral or bilateral cannula aimed at the BLA were trained on a contextual fear conditioning (CFC) task and 24 and 48 h later were given extinction training. Immediately following each extinction session they received intra-BLA infusions of the GABAergic antagonist bicuculline (50 ng), the beta-adrenocepter antagonist propranolol (500 ng), bicuculline with propranolol, norepinephrine (NE) (0.3, 1.0, and 3.0 microg), the GABAergic agonist muscimol (125 ng), NE with muscimol or a control solution. To investigate the involvement of the dorsal hippocampus (DH) as a possible target of BLA activation during extinction, other animals were given infusions of muscimol (500 ng) via an ipsilateral cannula implanted in the DH. Bilateral BLA infusions of bicuculline significantly enhanced extinction, as did infusions into the right, but not left BLA. Propranolol infused into the right BLA together with bicuculline blocked the bicuculline-induced memory enhancement. Norepinephrine infused into the right BLA also enhanced extinction, and this effect was not blocked by co-infusions of muscimol. Additionally, muscimol infused into the DH did not attenuate the memory enhancing effects of norepinephrine infused into the BLA. These findings provide evidence that, as with original CFC learning, noradrenergic activation within the BLA modulates the consolidation of CFC extinction. The findings also suggest that the BLA influence on extinction is not mediated by an interaction with the dorsal hippocampus.
Berlau
Daniel J
DJ
Center for the Neurobiology of Learning and Memory, Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-3800, USA. danb@uci.edu
McGaugh
James L
JL
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004777:Environment; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000502:physiology; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D018682:GABA Agents / Q000008:administration & dosage; D006624:Hippocampus / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D009118:Muscimol / Q000008:administration & dosage; D009638:Norepinephrine / Q000008:administration & dosage / Q000502:physiology*; D011433:Propranolol / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D004338:Drug Combinations; D018682:GABA Agents; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D011433:Propranolol; D009638:Norepinephrine; D001640:Bicuculline