Effects of sustained serotonin reuptake inhibition on the firing of dopamine neurons in the rat ventral tegmental area

• Published in: Journal of psychiatry & neuroscience Vol. 34; no. 3; pp. 223 - 229
• Main Authors: Dremencov, Eliyahu, PhD, El Mansari, Mostafa, PhD, Blier, Pierre, MD, PhD
• Format: Journal Article
• Language: English
• Published: Ottawa, ON Canadian Medical Association 01.05.2009; CMA Impact Inc; CMA Impact, Inc
• Subjects: Action Potentials - drug effects; Aminopyridines - administration & dosage; Analysis of Variance; Animals; Biological and medical sciences; Catheterization; Citalopram - administration & dosage; Depression, Mental; Dopamine; Dopamine - metabolism; Drug therapy; Electrophysiology; Fundamental and applied biological sciences. Psychology; Health aspects; Indoles - administration & dosage; Male; Medical Education; Medical sciences; Mental health; Meta-analysis; Microelectrodes; Neurons; Neurons - drug effects; Neurons - physiology; Neurotransmitters; Properties; Psychiatry; Psychoanalysis; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Rats; Rats, Sprague-Dawley; Research Papers; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists - administration & dosage; Serotonin uptake inhibitors; Serotonin Uptake Inhibitors - administration & dosage; Ventral Tegmental Area - drug effects; Ventral Tegmental Area - physiology; Netherlands; Dopamine; Rat; Serotonin; Psychology; Rodentia; Central nervous system; Catecholamine; Encephalon; Vertebrata; Mammalia; Neuron; Animal; Neurotransmitter; Inhibition; Psychopathology; Ventral tegmental area; Psychiatry
• ISSN: 1180-4882; 1488-2434

Background Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are efficacious in depression because of their ability to increase 5-HT neurotransmission. However, owing to a purported inhibitory effect of 5-HT on dopamine (DA) neuronal activity in the ventral tegmental area (VTA), this increase in 5-HT transmission might result in a suppression of the firing activity of DA neurons. Since the mesolimbic DA system plays an important role in motivation and reward, a potential decrease in the firing of DA neurons may lead, in some patients, to a lack of adequate response to SSRIs. Methods We administered the SSRIs citalopram or escitalopram in rats. We determined DA neuronal activity using in-vivo electrophysiology. Results Sustained administration of escitalopram robustly decreased the firing rate and burst activity of DA neurons. There was no difference in the mean number of spontaneously active DA neurons per tract among the 3 groups (citalopram, escitalopram, control). This inhibition was reversed by the selective 5-HT2C receptor antagonist SB 242084. Citalopram, however, did not alter the overall firing rate but inhibited the burst activity of DA neurons. Limitations Our experiments were carried out with the rats under general anesthesia. Therefore, under such conditions the absolute changes produced by SSRIs may heve been different from those occurring in freely moving rats. The exact location of the 5-HT2C receptors mediating the inhibitory effects of the SSRIs could not be determined in these studies.