Effects of the serotonin 5-HT7 receptor antagonist SB-269970 on the inhibition of dopamine neuronal firing induced by amphetamine

Using extracellular unitary recordings in anaesthetized rats, this study examined the implication of the serotonin 7 (5-HT7) receptors in the inhibitory effect of amphetamine on ventral tegmental area and substantia nigra pars compacta dopamine neuronal activity. The acute administration of the selective 5-HT7 receptor antagonist, SB-269970 (0.1, 0.5 and 1 mg/kg, i.p.), did not alter the firing activity of dopamine neurons. Interestingly, this antagonist prevented significantly the inhibition of dopamine neuronal firing activity induced by amphetamine (1 mg/kg, i.v.) in the ventral tegmental area, but not in the substantia nigra pars compacta. The present results suggest that 5-HT7 receptors modulate the dopamine firing activity in the ventral tegmental area, thus affecting preferentially the mesocorticolimbic pathway.