The role of dopamine and GABA in the frontal cortex of mice in modulating a motor-stimulant effect of amphetamine and cocaine.
The results of previous studies have indicated that the activation of dopaminergic and GABAergic systems in the prefrontal cortex can decrease dopaminergic and glutamatergic activity in the striatum, ostensibly by the inhibition of corticofugal glutamatergic pathways. The present studies were designed to investigate the cortical influence of dopamine and GABA agonists and antagonists on the motor response to systemically administered amphetamine and cocaine in the mouse. The results show that both dopamine and THIP, the GABA(A) agonist, injected intracortically (i.c.) depress amphetamine- or cocaine-induced stereotypy. That these responses are functionally significant is illustrated by the i.c. effects of sulpiride and bicuculline; they enhance the motor activity of the stimulants, suggesting that both dopaminergic and GABAergic systems in the cortex are activated by systemically administered amphetamine or cocaine. Additional experiments demonstrated that bicuculline i.c. can antagonize the depressant effect of dopamine i.c.; therefore, the dopaminergic inhibition in the cortex appears to be mediated by the activation of a cortical GABA system. These results show that systemically administered amphetamine or cocaine causes dopaminergic effects not only in the striatum but also in the cortex, and that the dopaminergic effect in the cortex may activate a cortical GABAergic system, which in turn, may account for the noted cortical inhibition of the dopaminergic motor-stimulatory action in the striatum.
Karler
R
R
Department of Pharmacology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Calder
L D
LD
Thai
D K
DK
Bedingfield
J B
JB
D000661:Amphetamine / Q000008:administration & dosage*; D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage; D003042:Cocaine / Q000008:administration & dosage*; D004298:Dopamine / Q000008:administration & dosage* / Q000502:physiology*; D018491:Dopamine Agonists / Q000008:administration & dosage; D018492:Dopamine Antagonists / Q000008:administration & dosage; D004347:Drug Interactions; D005625:Frontal Lobe / Q000187:drug effects* / Q000502:physiology*; D018755:GABA Agonists / Q000008:administration & dosage; D018756:GABA Antagonists / Q000008:administration & dosage; D007555:Isoxazoles / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008959:Models, Neurological; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D013469:Sulpiride / Q000008:administration & dosage; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018755:GABA Agonists; D018756:GABA Antagonists; D007555:Isoxazoles; D005680:gamma-Aminobutyric Acid; D013469:Sulpiride; D000661:Amphetamine; D003042:Cocaine; C015542:gaboxadol; D004298:Dopamine; D001640:Bicuculline