Differential Effects of Pharmacological Manipulations of Central α₁- and a₂-Adrenergic Receptors on the Secretion of Thyrotropin and Growth Hormone in Male Rats*

Disruption of Prepulse Inhibition after Stimulation of Central but not Peripheral α-1 Adrenergic Receptors

“…Previous studies with cirazoline have shown that systemic administration of this a1 agonist can also increase startle responses, although at a higher dose range than what was utilized in the present studies (Carasso et al, 1998;Varty et al, 1999). Further, systemic administration of the a2 adrenergic antagonist, yohimbine, which would increase NE tone, has been shown to facilitate acoustic startle amplitude in both humans and animals (Kehne and Davis, 1985;Krulich et al, 1982;Morgan et al, 1993). However, a recent study found no effect of yohimbine or another a2 antagonist, atipamezole, on startle (Powell et al, 2005), and, in the present studies, high systemic doses of phenylephrine and methoxamine actually decreased baseline startle magnitude.…”

“…Nonetheless, in order to confirm that a1 receptor-induced deficits in PPI are mediated by the CNS and not the periphery, the effects of a1 agonists with low blood-brain barrier permeability were also examined. When comparing the effects of central vs systemic administration of methoxamine and phenylephrine, two a1 agonists with low blood-brain barrier permeability (Holz et al, 1982;Krulich et al, 1982), it was found that both methoxamine and phenylephrine disrupted PPI when administered centrally, but not systemically. In the case of methoxamine, even a dose that was 30-fold higher than the effective central dose failed to disrupt PPI when given systemically, indicating that central and not peripheral a1 receptors mediate the effects of a1 adrenergic agonists on PPI.…”

Stimulation of Alpha‐Adrenoceptors Facilitates the Release of Growth Hormone‐Releasing Hormone from Rat Hypothalamus in vitro

“…Krulich et nl. (9) have reported that methoxamine inhibits GH release in the rat. However, these authors also reported that prazosin partially inhibited GH release induced by clonidine, and suggested that a,-adrenoceptors may be stimulatory.…”

“…Clonidine, a predominantly a2-adrenoceptor agonist, stimulates G H release in vivo (8); this effect is blocked by the a,-adrenoceptor antagonist yohimbine (8,9), and is abolished in the presence of antiserum to G H R H (lo), but not to somatostatin (9). This suggests that the a,-adrenoceptors are directly stimulatory to G H R H neurons.…”

“…Conversely, a,-adrenoceptor agonists such as methoxamine appear to inhibit G H release via somatostatin-mediated pathways (1 1). However, Krulich et al (9) found that the effect of clonidine on G H release was partially antagonized by the a ,-adrenoceptor antagonist prazosin, and suggested that both aI-and a,-adrenoceptors were involved in the stimulation of G H release. Part of the difficulty in discovering the precise sites and roles of adrenoceptors in regulating G H release has been the lack of a robust and reliable assay for rat GHRH which would allow for discrimination of the effects of adrenoceptors on GHRH directly.…”