Role of dopamine and GABA in the control of motor activity elicited from the rat nucleus accumbens.
The application of 1.2 and 12.0 micrograms/side of the GABAA receptor agonist 3-aminopropane sulphonic acid bilaterally into the nucleus accumbens (Acb) of rats nonsignificantly depressed locomotor activity as assessed in automated Animex activity cages, while the highest dose (60 micrograms/side) significantly stimulated activity. The GABAA receptor antagonists picrotoxinin (0.0625 and 0.125 micrograms/saide) and bicuculline (0.895 micrograms/side) produced forward locomotion around the cage accompanied by a number of other behaviours. The GABAB agonist baclofen (0.023 and 0.092 micrograms/side) induced a short-lasting (18 min) locomotor depression. None of the GABAB antagonists tested (2-hydroxysaclofen 2.6 micrograms/side, two novel beta-(benzo[b]furan) analogues of baclofen 9G or 9H each 6.8 micrograms/side, 4-aminobutylphosphonic acid 1.32 micrograms/side and phaclofen 0.535 and 2 micrograms/side) significantly affected locomotor activity. In rats pretreated with reserpine and alpha-methyl-p-tyrosine, picrotoxinin (0.0625 and 0.125 micrograms/side) did not significantly alter locomotor activity. Furthermore, when picrotoxinin (0.0625 micrograms/side) was combined with either the selective dopamine (DA) D1 agonist SKF38393 or the selective D2 agonist quinpirole, no significant alteration in locomotor function occurred. When SKF38393 and quinpirole were coadministered, significant stimulation occurred which was further enhanced by the addition of picrotoxinin. It is concluded that GABAA receptors, together with D1 and D2 receptors, play a major role in modulating the control of motor function by the Acb of rats.
Wong
L S
LS
Department of Pharmacology, University of Sydney, NSW, Australia.
Eshel
G
G
Dreher
J
J
Ong
J
J
Jackson
D M
DM
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists; D018756:GABA Antagonists; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D010852:Picrotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000145:classification / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D054830:Sesterterpenes; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D001418:Baclofen; D004298:Dopamine; D018492:Dopamine Antagonists; D018756:GABA Antagonists; D010852:Picrotoxin; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D054830:Sesterterpenes; D013654:Taurine; D005680:gamma-Aminobutyric Acid; C001355:tramiprosate; C022961:picrotoxinin