The effects of intranigral GABA and dynorphin A injections on striatal dopamine and GABA release: evidence that dopamine provides inhibitory regulation of striatal GABA neurons via D2 receptors.
The effects of injections of gamma-aminobutyric acid (GABA) and dynorphin A into the substantia nigra, pars reticulata on the levels of extracellular dopamine (DA) and GABA in the ipsilateral striatum of halothane-anaesthetized rats were studied using microdialysis. The effects of intranigral injections of substance P and neurokinin A were also studied. Intranigral GABA (300 nmol) or dynorphin A (0.5 nmol) injections produced a simultaneous decrease in DA and increase in GABA levels, while intranigral substance P (0.07 nmol) or neurokinin A (0.09 nmol) injections produced an increase in DA but had no effect on GABA levels. DA agonists, apomorphine (D1/D2), SKF 38393 (D1) and pergolide (D2) were applied locally by perfusing them through the microdialysis probe, each at a concentration of 10(-5) M. All 3 agonists decreased the levels of DA in the striatum. However, while apomorphine and SKF 38393 increased, pergolide decreased the levels of GABA in the striatum. The increase in striatal GABA produced by intranigral injections of GABA (300 nmol) was reversed by local perfusion with pergolide (10(-5) M), but was not reversed by local perfusion with SKF 38393 (10(-5) M). These findings suggest that D1 and D2 receptors differentially regulate striatal GABA release, and are stimulatory and inhibitory, respectively. Furthermore, it is suggested that nigrostriatal DA functions as an inhibitory modulator of striatal GABA neurons, acting via D2 receptors.
Reid
M S
MS
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
O'Connor
W T
WT
Herrera-Marschitz
M
M
Ungerstedt
U
U
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology*; D007839:Functional Laterality; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010477:Perfusion; D010479:Pergolide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2; D013238:Stereotaxic Techniques; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D010479:Pergolide; D005680:gamma-Aminobutyric Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D004399:Dynorphins; D001058:Apomorphine; D004298:Dopamine