Dopaminergic ventral tegmental neurons modulated by methylphenidate.
Treatment of psychostimulants leads to the development of behavioral sensitization, an augmented behavioral response to drug re-administration. The induction of behavioral sensitization to psychostimulants such as amphetamine and cocaine occurs at the ventral tegmental area's dopaminergic neurons (VTA-DA). Currently, there is limited experimental data about the physiological properties of methylphenidate (MPD) on VTA-DA neurons. Behavioral and electrophysiological experiments using male rats were performed before and after MPD treatment. The behavioral experiment included dose-response (0.6, 2.5, and 10.0 mg/kg MPD) study to select the most effective dose for the electrophysiological study. Methylphenidate increased locomotion in typical dose response characteristics. Based on this experiment, the 10.0 mg/kg MPD was used in two types of electrophysiological recordings: 1) intracellular recording of neuronal activity performed on horizontal 275-300 microm brain slices and 2) whole-cell patch clamping before and after electrical stimulation to study post-synaptic currents on neurophysiologically identified VTA-DA neurons. Methylphenidate suppressed the neuronal activity of these neurons for 210 +/- 30 sec. Stimulation of the prefrontal cortex afferent fibers to these VTA-DA neurons in the presence of TTX, saclofen, and picrotoxin led to the conclusion that this input is mediated via NMDA and kainate/AMPA receptors and may participate to induce behavioral sensitization to psychostimulants.
Prieto-Gomez
B
B
Departamento de Fisiologia, Divivion de Investigacion, Facultad de Medicina, Universidad Nacional Autonoma de Mexico Apdo, Postal 70250, Mexico 20, D.F., Mexico.
Benitez
M T
MT
Vazquez-Alvarez
A M
AM
Yang
P B
PB
Reyes Vazquez
C
C
Dafny
N
N
D000344:Afferent Pathways / Q000378:metabolism; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002648:Child; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D018756:GABA Antagonists / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism*
D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D008774:Methylphenidate; D004298:Dopamine