Iontophoretically administered drugs acting at the N-methyl-D-aspartate receptor modulate burst firing in A9 dopamine neurons in the rat.
Extracellular single-unit recording and iontophoresis were used to examine the effect of N-methyl-D-aspartate (NMDA) and the competitive NMDA antagonist (+/-)-4-(3-phosphonopropyl)-2-piperazine carboxylic acid (CPP) on the firing rate and firing pattern of A9 dopamine (DA) neurons in the rat. Administration of NMDA produced a dose-dependent increase in firing rate (up to nearly 300% of baseline at the highest ejection current), which could be blocked by iontophoretic CPP. Low currents (less than 10 nA) were sufficient to induce apparent depolarisation inactivation in some neurons. In addition to this effect on firing rate, NMDA also caused a dramatic increase in burst firing, which was also dose dependent; cells made more bursts, and each burst consisted of more spikes. The only measured aspect of burst morphology that was not affected was the mean burst interspike interval. All nonbursting cells (n = 10) were converted to burst firing by the drug. CPP administered alone was found to reduce burst firing, without affecting the firing rate. These data suggest that a tonically active excitatory amino acid input to A9 DA neurons is responsible for inducing burst firing in vivo and that this input seems to operate via the NMDA receptor, possibly by virtue of its link to a Ca2+ ionophore.
Overton
P
P
Department of Psychology, University of Reading, Berkshire, United Kingdom.
Clark
D
D
D000818:Animals; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D007478:Iontophoresis; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*
D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D004298:Dopamine