INVESTIGADORES
MARTIJENA Irene Delia
artículos
Título:
Increased fear learning coincides with neural dysinhibition and facilitated LTP in the basolateral amygdala following benzodiazepine withdrawal in rats.
Autor/es:
ISOARDI N.A., MARTIJENA I.D., CARRER H.F. AND V.A. MOLINA.
Revista:
Neuropsychopharmacology
Editorial:
Nature Publishing Group
Referencias:
Año: 2004 vol. 29 p. 1852 - 1864
ISSN:
0893-133X
Resumen:
Animals chronically administered with diazepam (DZM -- 2 mg/kg/day i.p.) or
vehicle (VEH) for 21 days were tested in a fear-conditioning paradigm 4 days
after the last administration. Increased freezing was observed in DZM withdrawn
rats as compared to VEH injected control rats in both associative and
nonassociative context and this increase was greatest for the DZM withdrawal
group in the paired context. In animals anesthetized with urethane, single
pulses in the medial prefrontal cortex evoked a field potential including a
population spike (PS) in the basolateral complex of the amygdala (BLA) of
control animals, whereas in DZM withdrawn animals multiple PSs were evoked. In
brain slices from control rats, stimulation of the external capsule evoked a
field potential including a PS in the BLA, whereas in DZM withdrawn rats
multiple PSs were evoked. The amplitude of the PS was smaller in slices obtained
from DZM withdrawn rats than from control rats, and paired pulse inhibition was
significantly less in the former. Perfusion with DZM 2 microM of slices obtained
from DZM withdrawn rats eliminated repetitive spiking. GABAergic blockade with
50 microM picrotoxin in control rats resulted in the appearance of multiple
secondary PSs. In slices from DZM withdrawn rats high-frequency stimulation
induced a highly significant potentiation that lasted at least 2 h (LTP),
whereas in control rats the same stimulation did not induce LTP. Neuronal
hyperexcitability leading to facilitated LTP observed in BLA of DZM withdrawn
rats could be due to depressed GABAergic activity (dysinhibition). The increased
synaptic plasticity may be at the root of the increased fear learning observed
in withdrawn animals.