Amphetamine- and cocaine-induced fos in the rat striatum depends on D2 dopamine receptor activation.
Amphetamine or cocaine injection causes expression of the immediate-early gene c-fos in the striatum. Previous studies have shown that dopamine D1 receptor activation is necessary for this effect, but have not established a consistent role for D2 receptors. We have investigated the involvement of D2 receptors in indirect dopamine agonist-induced striatal Fos-like immunoreactivity using the selective D2 antagonist eticlopride. Eticlopride treatment (0.5 mg/kg) caused Fos expression by itself, but also decreased Fos expression in the central striatum due to amphetamine (5.0 mg/kg) or cocaine (40 mg/kg) by 90% and 85%, respectively. In striatonigral neurons, identified by labeling with the retrograde tracer Fluorogold iontophoresed into the substantia nigra pars reticulata, the blockade of stimulant-induced Fos-like immunofluorescence by eticlopride was nearly complete, with decreases of 98% for amphetamine and 94% for cocaine. In striatonigral neurons, the D2 antagonist alone had minimal effect. We conclude that activation of both D1 and D2 receptor classes by dopamine agonists is necessary for induction of Fos in the striatonigral cells of normal rats. These results provide an important parallel to behavioral and electrophysiological work that also demonstrates D1/D2 interdependence in the control of normal basal ganglia functions.
Ruskin
D N
DN
Department of Psychobiology, University of California, Irvine 92717.
Marshall
J F
JF
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D008297:Male; D017072:Neostriatum; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*
D000662:Amphetamines; D016760:Proto-Oncogene Proteins c-fos; D017448:Receptors, Dopamine D2; D003042:Cocaine