Biology Reference
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injections to approximate 'binge' intoxication, it has been shown in rats that, during cocaine
withdrawal, the impact of rewarding brain stimulation is attenuated, as quantified by
alterations in intracranial self-stimulation (ICSS) behavior. These behavioral signs of
withdrawal were accompanied by enhancements of glutamatergic synaptic transmission
within the LA that occlude electrically induced LTP in brain slices. Synaptic enhancements
during periods of cocaine withdrawal were similar to LTP induced with electrical stimulation
in control slices, as both forms of synaptic plasticity involve an increase in glutamate release.
These results suggest that mechanisms of LTP within the amygdala are recruited during
withdrawal from repeated exposure to cocaine (Goussakov et al. 2006). As such, the authors
discuss the possibility that the development and maintenance of addictive behaviors may
involve, at least in part, mechanisms of synaptic plasticity within specific amygdala circuits.
Similar data we found in the LA after alcohol withdrawal of rats (Little et al. 2005;
Stephens et al. 2005). In rats, repeated episodes of alcohol consumption and withdrawal
(RWD) not only impair the formation of conditioned associations between discrete cues and
aversive unconditioned stimuli, but also reduced subsequent induction of LTP in EC - LA and
Schaffer collateral-hippocampal CA1 pathways. We speculate that reduced capacity for LTP
reflects RWD-induced synaptic saturation. Such synaptic strengthening might also allow
unconditioned stimuli access to pathways underlying previously-conditioned responses,
giving rise to broad stimulus generalization. Rats conditioned prior to RWD, but not controls,
showed generalization of conditioned fear from the training stimulus to a neutral control
stimulus, and a novel tone. These data indicate marked effects of binge-like drinking on
conditioning mechanisms, and suggest that such drinking patterns result in inappropriate
generalization of fear responses. In conclusion, repeated cycles of alcohol intoxication and
withdrawal such as are experienced by detoxified alcoholic patients, and even bouts of binge
drinking in social drinkers, have effects on neurotransmission that may account for increased
sensitivity to seizures in alcoholics undergoing detoxification and increased withdrawal-
induced anxiety.
B. Temporal lobe epilepsy
Temporal lobe epilepsy (TLE) is a common form of epilepsy and the amygdala is often
involved. TLE patients frequently show emotional disturbances ranging from mild fear to
pathological levels of anxiety and depression as well as memory impairment (Kalynchuk
2000). Kindling is a widely studied animal model of TLE in which daily electrical stimulation
of certain brain regions results in the gradual progression and intensification of limbic motor
seizures (Goddard et al. 1969). These recurrent seizures induced by repeated electrical
stimulation develop much faster in the amygdala than in the hippocampus (Goddard et al.
1969; McIntyre and Racine 1986). Although kindling has been extensively investigated in the
context of its clinical relevance to epilepsy, limited numbers of studies have investigated
plasticity changes after the kindling procedure. We have shown that kindling of the BLA
resulted in a significant impairment in the overall magnitude of LTP in the LA, the magnitude
of which was dependent on the number of prior stage V seizures. (Schubert et al. 2005). In
pilocarpine-treated rats we also found a reduced LA-LTP in comparison with sham-treated
controls. These data are in agreement with data obtained from tissue of TLE patients, showing
a strong suppression of NMDAR-dependent LTP in the dentate gyrus as compared to non-
