The Journal of Neuroscience, March 15, 2000, 20(6):2332-2345
Amphetamine Withdrawal Alters Bistable States and Cellular
Coupling in Rat Prefrontal Cortex and Nucleus Accumbens Neurons
Recorded In Vivo
Shao-Pii
Onn and
Anthony A.
Grace
Departments of Neuroscience and Psychiatry, University of
Pittsburgh, Pittsburgh, Pennsylvania 15260
Repeated amphetamine administration is known to produce changes in
corticoaccumbens function that persist beyond termination of drug
administration. We have found previously that long-term alteration in
dopamine systems leads to changes in gap junction communication,
expressed as dye coupling, between striatal neurons. In this study, the
cellular bases of amphetamine-induced changes were examined using
in vivo intracellular recordings and dye injection in
ventral prefrontal-accumbens system neurons of control and amphetamine-treated rats. Rats that had been withdrawn from repeated amphetamine displayed a significant increase in the incidence of dye
coupling in the prefrontal cortex and nucleus accumbens, which
persisted for up to 28 d after withdrawal. The increased coupling
was limited to projection neurons in both prefrontal cortical and
accumbens brain regions, as identified by their axonal trajectory or
the absence of interneuron-selective immunocytochemical markers. These
changes occurred with no substantial loss of tyrosine hydroxylase-immunoreactive terminals in these cortical and accumbens regions, ruling out dopamine degeneration as a precipitating factor. Previous studies showed that nitric oxide plays a role in the regulation of coupling; however, amphetamine-withdrawn rats had fewer
numbers of neurons and processes that stained for nitric oxide synthase
immunoreactivity. In amphetamine-treated rats, a higher proportion of
cortical cells fired in bursts, and a larger proportion of accumbens
and prefrontal cortical neurons exhibited bistable membrane
oscillations. By increasing corticoaccumbens transmission, amphetamine
withdrawal may lead to neuronal synchronization via gap junctions.
Furthermore, this adaptation to amphetamine treatment persists long
after the drug is withdrawn.
Key words:
addiction; psychostimulant; amphetamine; prefrontal
cortex; nucleus accumbens; electrophysiology; electrotonic
transmission; synchronization
Copyright © 2000 Society for Neuroscience 0270-6474/00/2062332-14$05.00/0
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