Acute and chronic administration of the selective 5‐HT_1A receptor antagonist WAY‐405 significantly alters the activity of midbrain dopamine neurons in rats: An in vivo electrophysiological study

Abstract

In this study, we examined the effect of the acute and chronic administration of WAY-405, a selective 5-HT(1A) receptor antagonist, on the number and firing pattern of spontaneously active substantia nigra pars compacta (A9) and ventral tegmental area (A10) dopamine (DA) neurons in anesthetized rats. This was accomplished using in vivo, extracellular single unit recording. The i.v. administration of WAY-405 (5-640 microg/kg) did not significantly alter the basal firing rate or pattern of spontaneously active A9 and A10 DA neurons. A single injection of 10 microg/kg of WAY-405 decreased the number of spontaneously active A10 DA neurons and the 100 microg/kg dose significantly decreased the number of spontaneously active A9 and A10 DA neurons compared to vehicle-treated animals. A single injection of 1, 10, or 100 microg/kg of WAY-405 significantly decreased the degree of bursting of A10 DA neurons. In contrast, 1 microg/kg i.p. of WAY-405 significantly increased the percent of A9 DA neurons exhibiting a bursting pattern. The repeated administration of 10 or 100 microg/kg i.p. of WAY-405 (21 days) significantly decreased the number of spontaneously active DA neurons in both the A9 and A10 compared to vehicle-treated animals and this decrease was not reversed by i.v. (+)-apomorphine. The repeated administration of WAY-405 significantly altered the firing pattern of DA neurons, particularly those in the A10 area. Overall, these results indicate that the antagonism of the 5-HT(1A) receptor significantly alters the activity of midbrain DA neurons in anesthetized rats.

Exploring the Role of 5-HT1A Receptors in the Regulation of Prepulse Inhibition in Mice: Implications for Cross-Species Comparisons

“…Indeed, C57Bl/6 mice have been shown to have low resting PPI compared to many other mouse strains, although this was not consistently seen in the present study when C57Bl/6 and Balb/c mice were compared (Figure ). The presence of 5-HT 1A receptors has been demonstrated in the ventral tegmental area (VTA) and administration of a selective 5-HT 1A receptor antagonist decreased the number of spontaneously active A10 DA neurons and their degree of bursting in this region . By antagonizing 5-HT 1A receptors, treatment with WAY100,635 might reduce mesolimbic dopamine release and, consequently, increase PPI similar to what has been shown with antipsychotic treatment in this strain .…”

“…The presence of 5-HT 1A receptors has been demonstrated in the ventral tegmental area (VTA) 37 and administration of a selective 5-HT 1A receptor antagonist decreased the number of spontaneously active A10 DA neurons and their degree of bursting in this region. 38 By antagonizing 5-HT 1A receptors, treatment with WAY100,635 might reduce mesolimbic dopamine release and, consequently, increase PPI similar to what has been shown with antipsychotic treatment in this strain. 39 The similarity of the effects of NAN-190 with those of WAY100,635 suggest that NAN-190 acts as a 5-HT 1A receptor antagonist in this environment.…”

A comparison of in vivo and in vitro neuroimaging of 5-HT1A receptor binding sites in the cat brain

“…It was notably reported that a subpopulation of 5-HT 1A receptors in the hypothalamus could play a regulatory role in neuroendocrine secretion (Osei-Owusu et al, 2005). Furthermore, electrophysiological studies have shown that selective 5-HT 1A receptor ligands modulate the activity of dopaminergic neurons in the substantia nigra (Dugast et al, 1998;Minabe et al, 2003). The data we have collected emphasize the heterogeneity of the distribution patterns of the 5-HT 1A receptors in the brain and could illustrate the diversity of their physiological functions.…”

Dissociation of rewarding and dopamine transporter-mediated properties of amphetamine

“…However, AMPH-induced increases in the firing rate of DA neurons may be more important for the development of addiction, and these appear only after repeated drug administration and are not related to effects of AMPH on the DAT. AMPH is a potent inhibitor of the serotonin transporter (37), and 5-HT is well known to be a strong modulator of DA neurotransmission, with various receptors causing different and often opposite effects (36,(38)(39)(40)(41)(42)(43)(44)(45). Therefore, a consideration of 5-HT receptors as candidates for the AMPH-induced increase in dopaminergic activity of DAT-KO mice may be promising.…”