Spinal modulation of acoustic startle: Opposite effects of clonidine and d-amphetamine

Abstract

Direct infusion of d-amphetamine (25--400 micrograms) or phenylephrine (12.5--50 micrograms) onto the spinal cord (intrathecal administration) increased acoustic startle amplitude. These effects were blocked by IP injection of the alpha 1-adrenergic antagonist WB-4101, but not the serotonin antagonist cyproheptadine. In contrast, intrathecal administration of clonidine (0.9--12.5 micrograms) markedly depressed startle. This effect was not blocked by IP administration of WB-4101 or cyproheptadine, but was blocked by IP or intrathecal administration of the alpha 2-adrenergic antagonist yohimbine (5 mg/kg), which by itself increased startle. Moreover, intrathecal yohimbine (100 micrograms) attenuated the depressant effect of IP clonidine, indicating that the spinal cord partially mediates the depressant effects on startle after systemic administration of clonidine. Thus clonidine does not behave like an alpha 1-agonist on acoustic startle, even when introduced directly onto the spinal cord. Conditions under which clonidine produces excitatory or depressant behavioral effects are discussed.

Elevated startle during withdrawal from acute morphine: a model of opiate withdrawal and anxiety

“…Conversely, the alpha 2 -antagonist yohimbine induces anxiety and elevates the startle response in humans and animals (Davis and Astrachan 1981;Morgan et al 1993).…”

Alpha2A-Adrenoceptors are Important Modulators of the Effects of D-Amphetamine on Startle Reactivity and Brain Monoamines

“…Earlier studies have shown that the a 2 -AR agonist clonidine decreases startle after systemic administration in humans (Kumari et al, 1996) and rats (Davis et al, 1977), and after spinal (Davis and Astrachan, 1981) or intra-amygdaloid (Schulz et al, 2002) administration in rats. The almost totally abolished startle reflex of WT mice after Dex 10 and especially 30 mg/kg was likely due to its sedative effect.…”

Apomorphine, d-amphetamine, strychnine and yohimbine do not alter prepulse inhibition of the acoustic startle reflex

“…It is known that the ~-adreuergic agonist clonidine markedly depresses acoustic startle (Fechter 1974b;Davis et al 1977) in a yohimbine-reversible manner (Davis and Astrachan 1981). In fact, activation of ~a-adrenergic receptors by clonidine is one of the most robust drug effects that has ever been described for startle.…”