Nitric oxide is involved in nicotine-induced burst firing of rat ventral tegmental area dopamine neurons.
In the present study, using single cell recordings in vivo and intracellular recordings in vitro from midbrain slices, the role of N-methyl-d-aspartate (NMDA) receptor signaling on firing activity in ventral tegmental area dopamine neurons elicited by nicotine was investigated in the rat. In accordance with previous studies, systemic nicotine (0.5 mg/kg s.c.) increased both firing rate and burst firing of dopamine neurons in vivo, and bath-applied nicotine (10 microM) increased firing rate in vitro. The competitive NMDA receptor antagonist CGP39551 (2.5 mg/kg i.p.) inhibited nicotine's effects on burst firing and also attenuated the nicotine-induced increase in firing rate. Moreover, although the nitric oxide (NO)-synthase inhibitor N-nitro-l-arginine-methyl-ester (l-NAME; 5.0 mg/kg i.p.) had no effect on cell firing by itself, it prevented the response to nicotine in vivo. In contrast, l-NAME (100 microM) did not influence nicotine's effect on dopamine cell firing in vitro, suggesting that the effect of l-NAME seen in vivo is dependent on presynaptic afferent input. The present study confirms previous results suggesting that the effect of systemically administered nicotine is in part presynaptic and mediated via NMDA receptors. The data also indicate that NO plays an important role in the previously demonstrated, indirect, glutamate-mediated excitation of these neurons by nicotine. By inference, our results provide additional support for the involvement of NO in nicotine dependence.
Schilström
B
B
Karolinska Institutet, Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Nanna Svartz väg 2, S-171 77 Stockholm, Sweden.
Mameli-Engvall
M
M
Rawal
N
N
Grillner
P
P
Jardemark
K
K
Svensson
T H
TH
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D005731:Ganglionic Stimulants; C064540:CGP 39551; D009569:Nitric Oxide; D009538:Nicotine; D015763:2-Amino-5-phosphonovalerate; D019331:NG-Nitroarginine Methyl Ester; D004298:Dopamine