The Journal of Neuroscience, May 1, 1999, 19(9):3594-3609
Striatal Neuronal Activity and Responsiveness to Dopamine and
Glutamate after Selective Blockade of D1 and D2 Dopamine Receptors in
Freely Moving Rats
Eugene A.
Kiyatkin and
George V.
Rebec
Program in Neural Science, Department of Psychology, Indiana
University, Bloomington, Indiana 47405
Although striatal neurons receive continuous dopamine (DA) input,
little information is available on the role of such input in regulating
normal striatal functions. To clarify this issue, we assessed how
systemic administration of selective D1 and D2 receptor blockers or
their combination alters striatal neuronal processing in freely moving
rats. Single-unit recording was combined with iontophoresis to monitor
basal impulse activity of dorsal and ventral striatal neurons and their
responses to glutamate (GLU), a major source of excitatory striatal
drive, and DA. SCH-23390 (0.2 mg/kg), a D1 antagonist, strongly
elevated basal activity and attenuated neuronal responses to DA
compared with control conditions, but GLU-induced excitations were
enhanced relative to control as indicated by a reduction in response
threshold, an increase in response magnitude, and a more frequent
appearance of apparent depolarization inactivation. In contrast, the D2
antagonist eticlopride (0.2 mg/kg) had a weak depressing effect on
basal activity and was completely ineffective in blocking the neuronal response to DA. Although eticlopride reduced the magnitude of the GLU
response, the response threshold was lower, and depolarization inactivation occurred more often relative to control. The combined administration of these drugs resembled the effects of SCH-23390, but
whereas the change in basal activity and the GLU response was weaker,
the DA blocking effect was stronger than SCH-23390 alone. Our data
support evidence for DA as a modulator of striatal function and suggest
that under behaviorally relevant conditions tonically released DA acts
mainly via D1 receptors to provide a continuous inhibiting or
restraining effect on both basal activity and responsiveness of
striatal neurons to GLU-mediated excitatory input.
Key words:
striatum; dopamine; glutamate; single-unit activity; iontophoresis; SCH-23390; eticlopride
Copyright © 1999 Society for Neuroscience 0270-6474/99/1993594-16$05.00/0
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