The electrophysiological effects of neurotensin on spontaneously active neurons in the nucleus accumbens: an in vivo study.
Considerable evidence obtained from neuroanatomical and neurochemical studies suggests an interaction between the endogenous tridecapeptide neurotensin (NT) and central nervous system dopamine (DA) neurons. Centrally administered NT blocks many of the actions of synaptic DA in limbic brain areas; the specific mechanism and receptors involved remain under investigation. The electrophysiological effects of NT were studied using extracellular recording techniques and iontophoretic application in 243 spontaneously active neurons in the nucleus accumbens (NAc), with a positive/negative waveform. NT was directly applied to 208 neurons in a pulsatile fashion by iontophoresis (21+/-1 nA). NT had no effect on the firing rate of 120 neurons ((0.31+/-0.72)%), decreased the firing rate in 51 neurons ((-27.87+/-1.52)%), and increased the firing rates of 37 neurons ((33.38+/-2.6)%). One hundred ninety nine (81.9%) of the neurons studied were sensitive to iontophoretically applied DA (>15% decrease in firing rate). The effects of continuous NT application on DA-induced inhibitions were studied in 169 neurons. NT attenuated neuronal responses to directly applied DA by (49.95+/-4.52)%, with antagonism in the "core" subregion (n=96) of (33.41+/-7.75)% when compared with antagonism in the "shell" subregion (n=71) of (61.39+/-5.2)%. The effects of NT on DA were consistent and independent of the effects of NT alone. These data provide further evidence that NT functions as a true neuromodulator in the NAc, exerting minimal direct effects, but blocking the actions of DA.
Stowe
Zachary N
ZN
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA.
Landry
Jacque C
JC
Tang
Zhongliang
Z
Owens
Michael J
MJ
Kinkead
Becky
B
Nemeroff
Charles B
CB
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism* / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism* / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018492:Dopamine Antagonists; D018377:Neurotransmitter Agents; D009496:Neurotensin; D004298:Dopamine