5‐Hydroxytryptamine 1A Receptors Inhibit Cold‐Induced Sympathetically Mediated Cutaneous Vasoconstriction in Rabbits

Abstract

Journal of PhysiologyIdentification of the different 5-hydroxytryptamine (5-HT) receptor subtypes has facilitated our understanding of the contribution of 5-HT to the regulation of body temperature. Activation of 5-HT 1A receptors decreases body temperature (Hjorth, 1985;Gudelsky et al. 1986;Cryan et al. 1999). Activation of 5-HT 2A receptors increases body temperature (Gudelsky et al. 1986;Löscher et al. 1990;Mazzola-Pomietto et al. 1995). However, the relevant neuroanatomical pathways and underlying neurotransmitter mechanisms mediating these effects remain to be elucidated. The task is especially complicated because 5-HT alters so many psychological, behavioural and physiological variables (Barnes & Sharp, 1999). Pharmacological and physiological studies of the mechanisms underlying the temperature effects of agents acting at 5-HT 1A receptors often focus on body temperature per se, without determining the relative contributions of heat production and/or heat loss to the temperature equation.Similar considerations apply to neuroanatomical studies. Interest in the role of 5-HT in temperature control has focused on upper brainstem and forebrain 5-HT-innervated regions. Much less attention has been paid to possible contributions of the thermoregulatory role of 5-HT via regulation of heat exchange with the environment through the cutaneous circulation, i.e. on heat dissipation rather than heat production. Even when temperature studies have focused on 5-HT neurons in the medullary raphe region, interpretation of the results has emphasized possible ascending projections of the cells (Dickenson, 1977;Berner et al. 1999), rather than descending projections to cutaneous sympathetic preganglionic neurons in the spinal cord. Central neuroanatomical organization of the descending central control of the cutaneous circulation includes a brainstem relay in raphe magnus/pallidus and the parapyramidal region of the medulla oblongata (Blessing & Nalivaiko, 2000;Nalivaiko & Blessing, 2001;Tanaka et al. 2002). Neurons in this medullary region include the B1-B3 bulbospinal cells that synthesize 5-HT (Loewy, 1981;Steinbusch, 1981;Skagerberg & Bjorklund, 1985;Nicholas et al. 1992). Transneuronal intra-axonal tracing experiments in rats show that 5-HT neurons are amongst

Activation of slowly conducting medullary raphé-spinal neurons, including serotonergic neurons, increases cutaneous sympathetic vasomotor discharge in rabbit

“…Stimulation of the midline medullary raphé (3 pulses, 10-ms interval, 0.5-ms duration, 100 -200 A) evoked discharge in the ear pinna sympathetic nerve with an onset latency of 259 Ϯ 6 ms [n ϭ 32 rabbits, including 21 animals used in the experiments reported in our previous papers (37,39,40) (Fig. 4A)].…”

“…The proximal end of a cut sympathetic nerve supplying an arterial vessel in ear pinna was placed across a pair of silver-wire electrodes and covered with a mixture of paraffin oil and vaseline (9,37,39,41). Multifiber nerve activity was recorded differentially using a Neurolog NL 100 preamplifier (gain, ϫ1), NL104 amplifier (gain, ϫ20,000), and NL125 filter (band pass between 100 Hz and 1 kHz) (Digitmer, Hertfordshire, UK).…”

“…Administration of 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a 5-HT 1A receptor agonist, markedly inhibits cold-activated cutaneous sympathetic vasomotor nerve discharge in rabbits, impairing the animal's ability to maintain body temperature in the cold (37). Similarly, systemically administered 8-OH-DPAT reverses cutaneous vasoconstriction occurring as part of the lipopolysaccharide-induced febrile response (5).…”

Defects in Breathing and Thermoregulation in Mice with Near-Complete Absence of Central Serotonin Neurons

“…Some 5-HT neurons project to the intermediolateral cell column (Cano et al, 2003), and increase their activity in response to both environmental (Martin-Cora et al, 2000) and hypothalamic (Nason and Mason, 2006) cooling. Additionally, systemic or raphé/parapyramidal application of the 5-HT 1A receptor agonist 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) decreases core temperature and impairs shivering (Hoffman et al, 2007), inhibits cold-induced vasoconstriction (Ootsuka and Blessing, 2003), and attenuates leptin-evoked activation of brown adipose tissue (BAT) sympathetic outflow (Morrison, 2004a). However, it remains unclear if 5-HT neurons are presympathetic motor neurons that drive thermogenesis and peripheral vasoconstriction, or if they simply modulate descending drive (Nason and Mason, 2006).…”

Role of serotonergic system in thermoregulation in rats

“…Selective agonists of 5HT1A receptors produce a considerable hypothermic response [33][34][35][36][37][38][39] . It was further shown that 5-HT1A receptor activation has effects on both heat loss 40,41) and heat production 34,35) . Not only 5-HT1A, but 5-HT3 and 5-HT7 have also captured the spotlight in recent years.…”