Serotonergic Modulation of Neuronal Activity in the Nucleus Accumbens Following Repeated Methamphetamine Administration in Rats

Abstract

Abstract. Electrophysiological studies were performed to determine whether serotonergic modulation in the nucleus accumbens (NAcc) was affected after repeated methamphetamine (MAP) administration. NAcc slices (400 mm) from Wistar rats administered MAP (5 mg/kg) or saline once daily for 5 days were prepared 1, 5, or 10 days after the final injection. Population spikes (PS) induced by local stimulation of NAcc were recorded. PS inhibition by serotonin was significantly attenuated in the MAP group at 5 days but did not differ at 1 or 10 days. We next analyzed the effects of serotonin receptor subtype (5-HT 1A,2,3,4,6,7 )-selective agonists of PS. Differences between saline and MAP groups in 5-HT 1A,2,3,4,6 receptor agonist-induced changes of PS were small or not significant. Interestingly, 5-HT 7 receptor agonists significantly enhanced PS in the MAP group. Changes in the secondary messenger system related to 5-HT 7 receptors were also investigated. Adenylate cyclase activator-induced PS enhancements were significantly larger in the MAP group. However, dibutyryl-cAMP-induced PS enhancement was not significantly different. In conclusion, 5-HT-induced inhibition of PS in NAcc was attenuated 5 days after repeated MAP treatment: the change in the effect of 5-HT was probably due to enhancement of the excitatory modulation via the 5-HT 7 receptor with adenylate cyclase signal transduction systems. [Supplementary Figure: available only at http://dx

5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders

“…5-HT 7 receptor agonists exerted slow depolarizing effects and increased neuronal firing in several brain areas (Figure 1), among which the anterodorsal nucleus of the rat thalamus (Chapin and Andrade, 2001), rat globus pallidus (Chen et al, 2008), mouse hippocampal CA1 region (Bickmeyer et al, 2002) and mouse trigeminal nucleus caudalis (Yang et al, 2014). Activation of 5-HT 7 receptors enhanced the firing rate of rat CA1 pyramidal neurons (Tokarski et al, 2003), CA3 pyramidal neurons (Gill et al, 2002), striatal cholinergic interneurons (Bonsi et al, 2007), prefrontal cortex pyramidal neurons (Zhang, 2003; Béïque et al, 2004a) and nucleus accumbens (NAc) neurons (Ishihara et al, 2013). In a spinal cord slice preparation, 5-HT application induced a locomotor-like rhythmic firing activity of motoneurons in wild type but not in 5-HT 7 KO mice, indicating that the excitability of spinal motoneurons was enhanced by 5-HT 7 receptors (Liu et al, 2009).…”