Depression of excitatory cortico-nucleus accumbens synaptic transmission in rat brain slices by dopamine, but not adenosine, depends upon intracortical mechanisms.
Extracellular field potentials, evoked by stimulation of the cortico-NAcc border, were recorded from the nucleus accumbens (NAcc) in horizontal slices of rat ventral forebrain. The peak amplitude of the population spike/excitatory postsynaptic potential complex (PEC, N2 component) was reduced by 78+/-2% ( n=44) by the antagonist of AMPA-type glutamate receptors, 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX, 10 microM). Dopamine (100 microM) reversibly depressed the peak amplitude of the PEC by 40+/-3% ( n=44). The GABA(A) receptor antagonists picrotoxin (10, 30 microM), or bicuculline methiodide (BMI, 20 microM), significantly reduced the PEC depression caused by dopamine (100 microM) to 9+/-3% ( n=20), 12+/-7% ( n=8) and 13+/-3% ( n=4) of control respectively, which, in the case of BMI, was reversible on washout of BMI. In slices with the frontal cortex removed (decorticated), dopamine (100 microM) was without effect on the PEC ( n=14). In contrast, the inhibition of the PEC by adenosine (by 40+/-9% in control, n=4), which was blocked by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 200 nM), was unaffected by picrotoxin (50 microM, n=4), and persisted in decorticated slices, albeit increased to 88+/-2% ( n=4) of control. These results indicate that the depression of the cortico-NAcc synaptic transmission by dopamine in this preparation is due to an action in frontal, possibly piriform, cortex, which may involve modulation of intracortical GABAergic circuitry. In contrast, depression by adenosine is consistent with a presynaptic action via A1 receptors on intra-NAcc glutamate-releasing terminals, although there may be an additional action of adenosine within the cortex that also influences the cortico-NAcc PEC.
Buckby
L E
LE
Department of Pharmacology, Division of Neuroscience, The Medical School, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK.
Lacey
M G
MG
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D004347:Drug Interactions / Q000502:physiology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D008297:Male; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D018047:Receptors, Purinergic P1; D005680:gamma-Aminobutyric Acid; D000241:Adenosine; D004298:Dopamine