5‐Hydroxytryptamine acts at 5‐HT2 receptors to decrease potassium conductance in rat nucleus accumbens neurones.

Abstract

SUMMARY1. Intracellular recordings were made from neurones in the nucleus accumbens in slices from the rat brain maintained in vitro.2. 5-Hydroxytryptamine (5-HT, 1-100 ,tM) depolarized 170 of 203 (84 %) neurones and caused them to discharge action potentials. The depolarization was associated with an increase in the input resistance, and was reversed in polarity by conditioning hyperpolarization; this reversal potential was linearly related to the logarithm of the extracellular potassium concentration.3. Application of 5-HT to neurones voltage-clamped near their resting potential (typically about -80 mV) caused an inward current and a decrease in the slope conductance. The current caused by 5-HT reversed polarity at the potassium equilibrium potential. Analysis with an equivalent circuit model of the neurone at steady state indicated that 5-HT selectively reduced the inward rectifier potassium conductance.4. The depolarization caused by 5-HT persisted in tetrodotoxin (1 ,1M). It was reduced but not abolished by a solution that contained lower levels of calcium (0'24 instead of 2-4 mM), higher levels of magnesium (5 instead of 1-2 mM), and cobalt (2 mM).5. The depolarization caused by 5-HT was competitively antagonized by the 5-HT2 antagonists ketanserin and mianserin with dissociation equilibrium constants of 3 and 45 nm respectively: spiperone (300 nM) also blocked the action of 5-HT. The depolarization was not mimicked or blocked by a number of other agonists and antagonists selective for the 5-HT1 and 5-HT3 receptor types.

Endogenous Serotonin Excites Striatal Cholinergic Interneurons via the Activation of 5-HT 2C, 5-HT6, and 5-HT7 Serotonin Receptors: Implications for Extrapyramidal Side Effects of Serotonin Reuptake Inhibitors

“…Of note, 5-HT has already been reported to exert an excitatory effect by suppressing K + conductances in other striatal neuronal subtypes (Stefani et al, 1990), as well as in nucleus accumbens neurons, subthalamic nucleus neurons, and cortical pyramidal neurons (North and Uchimura, 1989;Zhang, 2003;Xiang et al, 2005). In particular, in agreement with our data on striatal cholinergic interneurons, in other neuronal populations the excitatory responses to 5-HT2C receptor activation have been reported to be mediated by the closing of K + channels (Hsiao et al, 1997;Xiang et al, 2005).…”

“…A closure of K leak channels was shown to mediate the 5-HTinduced depolarization in dorsal vagal neurons (Hopwood and Trapp, 2005) and to be involved in the response of trigeminal and spinal cord motoneurons to 5-HT (Hsiao et al, 1997;Kjaerulff and Kiehn, 2001). In caudal raphe and nucleus accumbens and in motoneurons of the spinal cord, 5-HT has been reported to reduce Kir conductance (North and Uchimura, 1989;Bayliss et al, 1997;Kjaerulff and Kiehn, 2001). Interestingly, I Kir is involved in the regulation of the spontaneous firing activity of striatal cholinergic interneurons by counteracting a prominent HCN conductance (Wilson, 2005).…”

Actions of 5‐hydroxytryptamine and 5‐HT1A receptor ligands on rat dorso‐lateral septal neurones in vitro

“…The lack of effect of TFMPP as an agonist can be explained by the known low affinity for 5-HTIA receptors of this compound (pKD= 6.5;Hoyer, 1991 In approximately 30% of the neurones tested, 5-HT elicited a small depolarization, which followed the initial hyperpolarization. Similar depolarizations have been reported in hippocampal pyramidal cells (Andrade & Nicoll, 1987a;Colino & Halliwell, 1987), neurones in the nucleus accumbens (North & Uchimura, 1989), the medial prefrontal cortex (Araneda & Andrade, 1991), the cerebral cortex (Davies et al, 1987) and also in the lateral septal nucleus (Joels et al, 1987). As in the nucleus accumbens (North & Uchimura, 1989) and the prefrontal cortex (Araneda & Andrade, 1991), this 5-HT-induced depolarization of septal neurones was blocked by the 5-HT2/5-HTlc-receptor antagonist, ketanserin.…”

“…Similar depolarizations have been reported in hippocampal pyramidal cells (Andrade & Nicoll, 1987a;Colino & Halliwell, 1987), neurones in the nucleus accumbens (North & Uchimura, 1989), the medial prefrontal cortex (Araneda & Andrade, 1991), the cerebral cortex (Davies et al, 1987) and also in the lateral septal nucleus (Joels et al, 1987). As in the nucleus accumbens (North & Uchimura, 1989) and the prefrontal cortex (Araneda & Andrade, 1991), this 5-HT-induced depolarization of septal neurones was blocked by the 5-HT2/5-HTlc-receptor antagonist, ketanserin. This is in contrast to reports indicating that the depolarization observed in rat hippocampal neurones is not blocked by ketanserin but rather by putative 5-HT4-receptor antagonists (Andrade & Chaput, 1991).…”

Modulation of Neuronal Excitability by Serotonin-NMDA Interactions in Prefrontal Cortex

“…5-HT 1A receptor activation can induce a membrane hyperpolarization in hippocampal neurons (Andrade et al, 1986), probably by opening inward rectifying potassium channels (Colino and Halliwell, 1987), inhibiting voltage-dependent calcium channels (Penington and Kelly, 1990), or activating the TWIK-1 type of two-pore domain potassium channels (Deng et al, 2007). In contrast, 5-HT 2 receptor activation can induce a membrane depolarization in cortical neurons (Araneda and Andrade, 1991;Aghajanian and Marek 1997), probably by inhibiting an inwardly rectifying potassium conductance (North and Uchimura, 1989) or activating a cation nonselective current (Haj-Dahmane and Andrade, 1996).Since the activity of PFC pyramidal neurons encodes information storage in working memory (Goldman-Rakic, 1995), we would like to understand the role of 5-HT 1A and 5-HT 2A receptors on the excitability of these cells indicated by action potential (AP) firing. Studies on neuronal excitability usually use somatic injection of current pulses to directly depolarize membrane potential and elicit spikes.…”