Cellular effects of swim stress in the dorsal raphe nucleus

Abstract

Swim stress regulates forebrain 5-hydroxytryptamine (5-HT) release in a complex manner and its effects are initiated in the serotonergic dorsal raphe nucleus (DRN). The purpose of this study was to examine the effects of swim stress on the physiology of DRN neurons in conjunction with 5-HT immunohistochemistry. Basic membrane properties, 5-HT(1A) and 5-HT(1B) receptor-mediated responses and glutamatergic excitatory postsynaptic currents (EPSCs) were measured using whole-cell patch clamp techniques. Rats were forced to swim for 15min and 24h later DRN brain slices were prepared for electrophysiology. Swim stress altered the resting membrane potential, input resistance and action potential duration of DRN neurons in a neurochemical-specific manner. Swim stress selectively elevated glutamate EPSC frequency in 5-HT DRN neurons. Swim stress non-selectively reduced EPSC amplitude in all DRN cells. Swim stress elevated the 5-HT(1B) receptor-mediated inhibition of glutamatergic synaptic activity that selectively targeted 5-HT cells. Non-5-HT DRN neurons appeared to be particularly responsive to the effects of a milder handling stress. Handling elevated EPSC frequency, reduced EPSC decay time and enhanced a 5-HT(1B) receptor-mediated inhibition of mEPSC frequency selectively in non-5-HT DRN cells. These results indicate that swim stress has both direct, i.e., changes in membrane characteristics, and indirect effects, i.e., via glutamatergic afferents, on DRN neurons. These results also indicate that there are distinct local glutamatergic afferents to neurochemically specific populations of DRN neurons, and furthermore that these distinct afferents are differentially regulated by swim stress. These cellular changes may contribute to the complex effects of swim stress on 5-HT neurotransmission and/or the behavioral changes underlying the forced swimming test model of depression.

Presynaptic α4β2 Nicotinic Acetylcholine Receptors Increase Glutamate Release and Serotonin Neuron Excitability in the Dorsal Raphe Nucleus

“…Glutamate neurotransmission within the DRN has been implicated in the pathophysiology of affective disorders, such as depression (Paris and Cunningham, 1994;Grahn et al, 2000;Paul and Skolnick, 2003) and stress (Amat et al, 2005;Kirby et al, 2007). Indeed, in humans and animal models, glutamate receptor antagonists have been reported to be effective antidepressants (Trullas and Skolnick, 1990;Yilmaz et al, 2002).…”

Distinct Neurochemical and Functional Properties of GAD67-Containing 5-HT Neurons in the Rat Dorsal Raphe Nucleus

“…Subdivisions of the DRN innervate distinct targets and receive disparate afferent inputs (Abrams et al, 2004;Lee et al, 2005Lee et al, , 2007Hale et al, 2008), including 5-HTergic interactions within the DRN (Lemos et al, 2006;Kirby et al, 2007). Neurons in the DRL have been deemed to play a distinctive, crucial role in the response to stressors.…”

Stress-Hyperresponsive WKY Rats Demonstrate Depressed Dorsal Raphe Neuronal Excitability and Dysregulated CRF-Mediated Responses

“…The behavioral studies demonstrated differences in all three major monoaminergic systems; that is, dopamine, norepinephrine, and serotonin (Conti et al, 1997;Lopez-Rubalcava and Lucki, 2000;Pare and Tejani-Butt, 1996;Pearson et al, 2006;Tejani-Butt et al, 1994). The DRN is critical in mediating responses to uncontrollable stress (Maier and Watkins, 2005) and is functionally altered following in vivo stressor exposure (Kirby et al, 2007;Price et al, 2002). We, therefore, focused our attention to differences in mRNA expression, protein expression, and physiology in the DRN of WKY rats.…”