GABAA receptors in the mediodorsal thalamus play a crucial role in rat shell-specific acetylcholine-mediated, but not dopamine-mediated, turning behaviour.
The role of GABA(A) receptors in the mediodorsal thalamus (mdT) in turning behaviour of rats was studied. Neither the GABA(A) receptor agonist muscimol (50 ng) nor the antagonist bicuculline (200 ng) unilaterally injected into the mdT elicited any behavioural change. Unilateral injection of the acetylcholine receptor agonist (carbachol, 5 microg) into the nucleus accumbens shell has been found to elicit contraversive circling while unilateral injection of a mixture of dopamine D(1) ((+/-)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol [SKF 38393], 5 microg) and D(2) (quinpirole, 10 microg) receptor agonists into the same site is known to elicit contraversive pivoting. The contraversive circling induced by unilateral injection of carbachol (5 microg) into the nucleus accumbens shell was dose-dependently inhibited by muscimol (25 and 50 ng) injected into the mdT. This inhibitory effect of muscimol (50 ng) was antagonised by co-administration of bicuculline (200 ng), which alone did not modify the contraversive circling induced by carbachol (5 microg). The contraversive pivoting induced by unilateral injection of a mixture of SKF 38393 (5 microg) and quinpirole (10 microg) into the nucleus accumbens shell was inhibited by muscimol (25 and 50 ng) injected into the mdT, whereas bicuculline (200 ng) injected into the mdT did not significantly modify the pivoting. The inhibitory effect of muscimol (50 ng) on the pivoting induced by a mixture of SKF 38393 (5 microg) and quinpirole (10 microg) was not dose-dependent and not antagonised by bicuculline (200 ng). The present study suggests that GABA(A) receptors in the mdT play a limited role in spontaneously occurring locomotor activity. Secondly, this study demonstrates that GABA(A) receptors in the mdT transmit accumbens-dependent cholinergic circling, but not accumbens-dependent dopaminergic pivoting, to other brain structures. Finally, the present study shows that muscimol-sensitive, non-GABA(A) receptors in the mdT influence the accumbens-dependent dopaminergic pivoting. To what extent GABA(B) receptors in the mdT mediate the muscimol-induced effects upon the dopaminergic pivoting behaviour requires additional research.
Ikeda
H
H
Department of Pharmacology, Nihon University School of Dentistry, Tokyo, Japan. ikeda-h@dent.nihon-u.ac.jp
Kotani
A
A
Lee
J
J
Koshikawa
N
N
Cools
A R
AR
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000008:administration & dosage; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage; D002217:Carbachol / Q000008:administration & dosage; D018679:Cholinergic Agonists / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000008:administration & dosage; D018756:GABA Antagonists / Q000008:administration & dosage; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009118:Muscimol / Q000008:administration & dosage; D019257:Quinpirole / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D013788:Thalamus / Q000187:drug effects / Q000502:physiology*
D018679:Cholinergic Agonists; D018491:Dopamine Agonists; D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D019257:Quinpirole; D009118:Muscimol; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D002217:Carbachol; D000109:Acetylcholine; D004298:Dopamine; D001640:Bicuculline