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

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.