Injections of the selective adenosine A2A antagonist MSX-3 into the nucleus accumbens core attenuate the locomotor suppression induced by haloperidol in rats.
There is considerable evidence of interactions between adenosine A2A receptors and dopamine D2 receptors in striatal areas, and antagonists of the A2A receptor have been shown to reverse the motor effects of DA antagonists in animal models. The D2 antagonist haloperidol produces parkinsonism in humans, and also induces motor effects in rats, such as suppression of locomotion. The present experiments were conducted to study the ability of the adenosine A2A antagonist MSX-3 to reverse the locomotor effects of acute or subchronic administration of haloperidol in rats. Systemic (i.p.) injections of MSX-3 (2.5-10.0 mg/kg) were capable of attenuating the suppression of locomotion induced by either acute or repeated (i.e., 14 day) administration of 0.5 mg/kg haloperidol. Bilateral infusions of MSX-3 directly into the nucleus accumbens core (2.5 microg or 5.0 microg in 0.5 microl per side) produced a dose-related increase in locomotor activity in rats treated with 0.5 mg/kg haloperidol either acutely or repeatedly. There were no overall significant effects of MSX-3 infused directly into the dorsomedial nucleus accumbens shell or the ventrolateral neostriatum. These results indicate that antagonism of adenosine A2A receptors can attenuate the locomotor suppression produced by DA antagonism, and that this effect may be at least partially mediated by A2A receptors in the nucleus accumbens core. These studies suggest that adenosine and dopamine systems interact to modulate the locomotor and behavioral activation functions of nucleus accumbens core.
Ishiwari
Keita
K
Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
Madson
Lisa J
LJ
Farrar
Andrew M
AM
Mingote
Susana M
SM
Valenta
John P
JP
DiGianvittorio
Michael D
MD
Frank
Lauren E
LE
Correa
Merce
M
Hockemeyer
Jörg
J
Müller
Christa
C
Salamone
John D
JD
D058917:Adenosine A2 Receptor Antagonists; D000704:Analysis of Variance; D000818:Animals; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006220:Haloperidol / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects*; D011355:Prodrugs / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk / Q000187:drug effects; D043705:Receptor, Adenosine A2A / Q000502:physiology; D014970:Xanthines / Q000008:administration & dosage / Q000494:pharmacology*
D058917:Adenosine A2 Receptor Antagonists; D018492:Dopamine Antagonists; C113602:MSX 3 compound; D011355:Prodrugs; D043705:Receptor, Adenosine A2A; D014970:Xanthines; D006220:Haloperidol