Role of ventrolateral medulla in sympatholytic effect of 8-OHDPAT in rats

Abstract

In halothane-anesthetized, paralyzed, and artificially ventilated rats, the putative 5-hydroxytryptamine1A receptor agonist 8-OHDPAT (13.1 micrograms/kg iv) produced hypotension (-14.6 +/- 1.3 mmHg, n = 35), reduced lumbar sympathetic nerve discharge (SND, -17.8%, n = 35), and slowed the discharge rate of sympathoexcitatory neurons recorded in the rostroventrolateral medulla (RVLM, -17.6%, n = 20). The gain of the baroreflex was unaffected by the drug, but SND and RVLM unit discharges were silenced at significantly reduced levels of mean arterial pressure (MAP; 153 vs. 171 mmHg for SND, 155 vs. 172 mmHg for RVLM cells). Subsequent intravenous administration of the alpha 2-adrenergic receptor agonist clonidine (5.3 micrograms/kg) produced an additional decrease in MAP (-21.2 +/- 1.9 mmHg, n = 24) and SND (-24%, n = 24), Bilateral microinjections of 8-OHDPAT into the RVLM (1 nmol/side, n = 9) or into the raphe pallidus-obscurus (2 injections of 1 nmol each, n = 7) also produced hypotension (-22.9 +/- 3.2 and -14.4 +/- 2.8 mmHg, respectively) and sympathoinhibition (-39.1 and -24.6%, respectively). Bilateral microinjection into RVLM of the alpha 2-adrenergic antagonists idazoxan (16 nmol/side, n = 6) or rauwolscine (2 nmol/side, n = 6) attenuated the sympatholytic effect of both 8-OHDPAT (13.1 micrograms/kg, iv) and clonidine (5.3 micrograms/kg iv). These results suggest that 8-OHDPAT may exert a portion of its central sympatholytic effect by activating alpha 2-adrenergic receptors in the rostroventral medulla.

Activation of 5-HT1Areceptors in medullary raphé disrupts sleep and decreases shivering during cooling in the conscious piglet

“…In regions that do not contain 5-HT neurons, it is reasonable to postulate that any actions would be due to activation of inhibitory heteroreceptors located on non-5-HT neurons. Thus, in experiments in which 8-OH-DPAT was microinjected into the rostral ventrolateral medulla, a region containing few, if any, 5-HT neurons, the resulting decrease in blood pressure was most likely secondary to activating postsynaptic 5-HT 1A receptors expressed by non-5-HT neurons (46,62). In the rat, it appears that ϳ30 -43% of neurons in the raphé pallidus and raphé obscurus that express 5-HT 1A receptors are serotonergic, implying that, in these regions, more than one-half of the neurons expressing 5-HT 1A receptors are nonserotonergic (31).…”

Involvement of medullary serotonergic groups in multiple system atrophy

“…7,13 Serotonin, acting via different receptor subtypes, may either increase or decrease activity of sympathetic preganglionic neurons. 6 Thus, serotonergic inputs may influence sympathetic outflow both at medullary and spinal levels.…”

Buspirone Raises Blood Pressure through Activation of Sympathetic Nervous System and by Direct Activation of α1-Adrenergic Receptors after Severe Hemorrhage

“…The sympathoinhibitory effect of 5-HT1A agonists is well documented (Laubie et al, 1989;Nosjean and Guyenet, 1991). 5-HT1A receptors are coupled to the Gi/Go/Gz family of inhibitory G proteins (Albert et al, 1996;.…”

“…Activation of 5-HT1A receptors normally leads to hyperpolarization of neurons (Bobker and Williams, 1989). Indeed, the sympathoinhibitory response to systemic 5-HT1A receptor agonist administration in euvolemic animals is likely due to activation of postsynaptic 5-HT1A receptors expressed by bulbospinal neurons of the rostral ventrolateral medulla that normally provide tonic excitatory input to preganglionic sympathetic neurons (Nosjean and Guyenet, 1991;Bago et al, 1999). It is possible that the atypical sympathoexcitatory response to 5-HT1A receptor agonists observed during hemorrhage results from hyperpolarization of an alternative population of cells that provides inhibitory synaptic input to rostral ventrolateral medulla premotor neurons or some other population of presympathetic neurons during severe hypovolemia.…”