Acute and repeated administration of the selective 5-HT2A receptor antagonist M100907 significantly alters the activity of midbrain dopamine neurons:An in vivo electrophysiological study

We examined the effect of the acute and repeated administration of M100907 (formerly MDL 100907), a selective 5-HT2A receptor antagonist, on spontaneo usly active dopamine (DA) neurons in the substantia nigra pars compacta (SN C) and ventral tegmental area (VTA) of rats. This was accomplished using in vivo, extracellular single unit recording. The i.v. administration of M100 907 (0.01-0.64 mg/kg) did not significantly alter the basal firing rate or pattern of spontaneously active SNC and VTA DA neurons. A single injection of either 0.01 or 0.03 mg/kg i.p. of M100907 did not significantly alter th e number of spontaneously active DA neurons in either the SNC or VTA areas. However, 0.1 mg/kg i.p. of M100907 significantly increased the number of s pontaneously active SNC and VTA DA neurons compared to vehicle-treated anim als. A single injection of all doses of M100907 significantly decreased the degree of bursting in VTA DA neurons, whereas the 0.1 mg/kg dose increased the degree of bursting in SNC DA neurons. The repeated administration (one injection per day for 21 days) of 0.03 and 0.1 mg/kg i.p. of M100907 produ ced a significant decrease in the number of spontaneously active SNC and VT A DA neurons compared to vehicle-treated animals. The repeated administrati on of M100907 did not significantly alter the firing pattern of VTA DA neur ons but significantly altered the firing pattern of SNC DA neurons. The res ults of this study indicate that M100907 administration alters the activity of midbrain DA neurons in anesthetized rats. Synapse 40:102-112, 2001, (C) 2001 Wiley-Liss, Inc.