Cocaine-Related Disorders Clinical Trial
Official title:
Acoustic Startle Reduction In Cocaine Dependence
Chronic cocaine administration leads to changes in brain function that persist long after the
acute withdrawal phase. The acoustic startle response (ASR) is a well characterized reflexive
response to a sudden acoustic stimulus. The ASR is mediated by a simple 3-synapse subcortical
circuit; it is modulated in part by brain areas and neurotransmitters associated with cocaine
administration. Our initial study and subsequent replication reveals a profound diminution of
the ASR in cocaine-dependent subjects after a brief period of abstinence. Our preliminary
findings indicate that first degree relatives of cocaine-dependent subjects also have reduced
startle compared to healthy controls. The findings of low ASR in rats and humans during
cocaine washout and low ASR in family members suggests there may be both a trait and state
component of the startle reductions we have reported.
The central objectives of this proposal are to dissect this finding with regard to its
development and persistence in early and later phases of cocaine abstinence in humans; to
ascertain whether startle reduction and its potential normalization during later abstinence
is a predictor of clinical course in human subjects with cocaine dependence; and to examine
whether startle reduction is, at least in part, a vulnerability trait for the development of
cocaine dependence. This latter Aim will be carried out in humans by testing siblings of
cocaine-dependent subjects.
Cocaine dependence is an enormous public health problem. The significance of this work lies
in the potential for the ASR reduction to serve as a reliable, easily repeatable biological
measure of cocaine-induced brain changes that may enhance outcome prediction so that tailored
treatments may be directed at those patients most vulnerable to relapse, given the
restriction of resources for available for substance abuse treatment.
n/a
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