Effect of Physical Exercise and Acute Escitalopram on the Excitability of Brain Monoamine Neurons: In Vivo Electrophysiological Study in Rats

Abstract

Background: The antidepressant effect of physical exercise has been reported in several clinical and animal studies. Since serotonin, norepinephrine, and dopamine play a central role in depression, it is possible that the beneficial effects of physical exercise are mediated via monoamine pathways. This study investigates the effects of voluntary wheel running on the excitability of monoamine neurons.

Materials and methods: Male Sprague-Dawley rats were used in the study. Voluntary wheel running (VWR) rats were housed in individual cages with free access to a running wheel, while control animals were housed in standard laboratory cages. After three weeks, the rats were anesthetized, and in vivo electrophysiological recordings were taken from dorsal raphe nucleus serotonin neurons, locus coeruleus norepinephrine neurons, and ventral tegmental dopamine neurons.

Results: VWR stimulated activity in serotonin, but not in norepinephrine or dopamine neurons. Subsequently, acute administration of the selective serotonin reuptake inhibitor escitalopram in control rats led to complete suppression of serotonin neurons; this suppression was reversed by subsequent administration of selective antagonist of serotonin-1A receptors, WAY100135. Escitalopram induced only partial inhibition of serotonin neurons in the VWR rats while WAY100135 increased the firing activity of serotonin neurons above the baseline value.

Conclusions: The beneficial effect of physical exercise on mood is mediated, at least in part, via activation of serotonin neurons. Physical exercise can potentiate the response to selective serotonin reuptake inhibitors by increasing the basal firing activity and diminishing selective serotonin reuptake inhibitor-induced inhibition of serotonin neurons.

Keywords: Voluntary wheel running (VWR) rats; dopamine; norepinephrine; selective serotonin reuptake inhibitors (SSRIs); serotonin (5-HT).

Figure 1.

Characteristics of voluntary wheel running (VWR). (A) Daily running distances. (B) Running time. (C) Average running speed. *P<.05 in comparison with day 1 value (Bonferroni posthoc test).

Figure 2.

The effect of voluntary wheel running (VWR) on serotonin (5-HT), norepinephrine (NE), and dopamine (DA) neuron spontaneous firing activity. (A) Representative recording from a spontaneously active 5-HT neuron from the dorsal raphe nucleus of a control rat. (B) Representative recording from a spontaneously active 5-HT neuron from the dorsal raphe nucleus of a VWR rat. (C) Average firing rates of 5-HT, NE, and DA neurons in control and VWR rats. *P<.05, 2-tailed Student’s t test. Note: Since an extracellular recording technique was used, the amplitude of the action potentials on the panels A and B does not correspond to the actual membrane potential of the neurons.

Figure 3.

The effect of acute administration of escitalopram on the serotonin (5-HT) neuronal firing activity in control and voluntary wheel running (VWR) rats. (A) Effects of escitalopram and WAY 100135 on a representative 5-HT neuron from the dorsal raphe nucleus of a control rat. (B) Effects of escitalopram and WAY 100135 on a representative 5-HT neuron from the dorsal raphe nucleus of a VWR rat. (C) The effect of escitalopram on the average firing rates of 5-HT neurons in control and VWR rats, expressed as percent of baseline (mean±SEM); *P<.05 (Bonferroni posthoc test). Note: Since an extracellular recording technique was used, the amplitude of the action potential on the panels A and B does not correspond to the actual membrane potentials of the neurons.