Effects of physical training on functional activity of 5-HT 1B receptors in rat central nervous system: role of 5-HT-moduline

Abstract

The effect of physical exercise was examined on the sensitivity of 5-HT1B receptors and on 5-HT-moduline tissue concentration in the central nervous system of rats. Rats were trained for 7 consecutive weeks to run on a treadmill. Three groups of animals were selected: group 1, sedentary rats (controls); group 2, animals running for 1 h at 18 m/min for 5 days per week (moderate training) and group 3, animals running for 2 h, at 30 m/min on a 7% grade for 5 days per week (intensive training). The animals were sacrificed 24 h after the last running. Rat brains were dissected out to obtain hippocampus and substantia nigra and kept at -80 degrees C until use. 5-HT1B receptor activity was determined by studying [35S]GTPgammaS binding in a substantia nigra membrane preparation from individual animals, after stimulation by a selective 5-HT1B receptor agonist (CP 93,129). 5-HT-moduline tissue content in hippocampus from individual animals was determined by ELISA using a polyclonal anti-5-HT-moduline antibody. In moderately trained animals (n=5), the CP 93,129-stimulated [35S]GTPgammaS binding curve was shifted to the right compared with controls (n=6), whereas the binding was totally suppressed in intensely trained animals (n=5). In parallel, 5-HT-moduline tissue concentration in the hippocampus was slightly increased in moderately trained animals (117.3 +/- 8.9%) (n=5), whereas it was significantly increased in intensely trained animals (182.6 +/- 29.5%) (n=5) compared to controls (100 +/- 6.11%) (n=6). These results show that 5-HT1B receptors are slightly desensitized in moderately trained animals and totally desensitized in intensely trained animals; moreover, they suggest that the observed desensitization is related to an increase of 5-HT-moduline tissue content; this mechanism may play a role in various pathophysiological conditions.

Developmental profiles of neurotransmitter receptors in respiratory motor nuclei

“…An alternative possibility is that 5-HT 1B receptors expressed in motoneurons presynaptically control transmitter release at the motor plate level (D'Agostino et al, 2006). Broadly supportive of this are the findings that 5-HT 1B receptor expression declines in the brain in response to physical training (Chennaoui et al, 2000). There is also evidence that 5-HT 1B receptors carry trophic and other signals during embryonic and postnatal development both in the brain and peripheral nervous system (Nebigil et al, 2001).…”

Exercise Benefits Brain Function: The Monoamine Connection

“…Four weeks of moderate treadmill exercise decreases the levels of 5-HT without affecting the metabolism of 5-HT in the hippocampus [111]. On the contrary, seven days of high-intensity treadmill exercise significantly increases the levels of hippocampal 5-HT [112]. Furthermore, four-week moderate treadmill exercise does not change 5-HT concentration in the amygdala [111].…”

“…Maternal separation-induced depression-like behaviors and elevation of the hippocampal 5HT 1A receptor levels can be recovered by chronic wheel running [115]. Elevated levels of 5-HT 1B receptor activity in the hippocampus have been reported in rats subjected to one week of moderate treadmill exercise [112]. Higher levels of 5-HT 1B receptor in the hippocampus have been associated with resistance to electric stimulation-elicited learned helplessness [116].…”

“…Animals that are subjected to exercise perform better in the acquisition of conditioned learning tasks than their respective controls [111,127]. The improved learning performance induced by exercise is associated with downregulation of 5-HT 1A receptor and/or upregulation of 5-HT 2A in the hippocampus [111,112,128]. An inhibition of the G i receptor (e.g., 5-HT 1A ) activity and/or a stimulation of the G s receptor (e.g., 5-HT 2A ) activity result in elevation of the levels of cAMP, which is critical for the process of learning and memory.…”

Effects of exercise on gene expression in the central nervous system

“…For example, investigators have already shown that exercise alters the function of the nervous system at multiple levels by influencing gene expression (Cotman & Berchtold, 2002;O'Neal, Van Hoomissen, Holmes, & Dishman, 2001), protein synthesis (Eilam, Pinkas-Kramarski, Ratzkin, Segal, & Yarden, 1998;Gomez-Pinilla, Ying, Roy, Molteni, & Edgerton, 2002;Gomez-Pinilla, Ying, Opazo, Roy, & Edgerton, 2001;Irwin et al, 2000), cellular metabolism (McCloskey, Adamo, & Anderson, 2001), neuronal firing rate (Jacobs & Fornal, 1999;Rasmussen, Morilak, & Jacobs, 1986), neurotransmitter level (Dunn, Reigle, Youngstdet, Armstrong, & Dishman, 1996) and release (Meeusen, Piacentini, & DeMeirleir, 2001;Soares et al, 1999), receptor level (Yoo, Tackett, Crabbe, Bunnell, & Dishman, 2000), receptor function (Chennaoui et al, 2000), and CNS morphological characteristics (Churchill et al, 2002). The answer to this question is multifaceted and depends upon what level of CNS function is of interest.…”