Distinct Mechanisms of Ethanol Potentiation of Local and Paracapsular GABAergic Synapses in the Rat Basolateral Amygdala
JPET 324:251-260, 2008
Converging lines of behavioral and pharmacological evidence
suggest that GABAergic synapses in the basolateral amygdala
(BLA) may play an integral role in mediating the anxiolytic
effects of ethanol (EtOH).
Since anxiety is thought to play
an important role in the development of, and relapse to, alcoholism,
elucidating the mechanisms through which EtOH modulates GABAergic
synaptic transmission in the BLA may be fundamental in understanding
the etiology of this disease.
A recent study in mice has shown
that principal cells within the BLA receive inhibitory input
from two distinct types of GABAergic interneurons: a loosely
distributed population of local interneurons and a dense network
of paracapsular (pcs) GABAergic cells clustered along the external
Here, we sought to confirm the presence of these
two populations of GABAergic synapses in the rat BLA and evaluate
their ethanol sensitivity.
Our results suggest that rat BLA
pyramidal cells receive distinct inhibitory input from local
and pcs interneurons and that EtOH potentiates both populations
of synapses, albeit via distinct mechanisms. EtOH enhancement
of local inhibitory postsynaptic currents (IPSCs) was associated
with a significant decrease in paired-pulse ratio (PPR) and
was significantly potentiated by the GABAB
SCH 50911 [(+)-(S
)-5,5-dimethylmorpholinyl-2-acetic acid], consistent
with a facilitation of GABA release from presynaptic terminals.
Conversely, EtOH enhancement of pcs IPSCs did not alter PPR
and was not enhanced by SCH 50911 but was inhibited by blockade
of noradrenergic receptors.
Collectively, these data reveal
that EtOH can potentiate GABAergic inhibitory synaptic transmission
in the rat BLA through at least two distinct pathways.Read Full Abstract
Request Reprint E-Mail: email@example.com