To study the species difference of guinea pigs and rats in response to
5-hydroxytryptophan (5-HTP), we injected both animals intracisternally with
5,7-dihydroxytryptamine. In rats with
5,7-dihydroxytryptamine lesions,
5-HTP evoked the well described myoclonic-serotonergic syndrome. In the guinea pig,
5,7-dihydroxytryptamine lesions significantly increased the severity of myoclonic response to
5-HTP (150 mg/kg) compared to vehicle controls, resulting in lethal convulsions. Guinea pigs treated with
5,7-dihydroxytryptamine did not develop spontaneous
myoclonus, or when treated with
5-HTP, other 'serotonergic behaviors' such as lateral head weaving, hindlimb abduction, and forepaw tapping. Guinea pigs tolerated intracisternal
5,7-dihydroxytryptamine less well than rats, with a higher mortality, although immediate post-injection convulsions were less severe and did not require
phenobarbital prophylaxis. Staged lower doses of
5,7-dihydroxytryptamine (100-200 micrograms) were better tolerated than a single high dose of
neurotoxin (400 micrograms). The regional profile of
5,7-dihydroxytryptamine lesions in the guinea pig resembled that of the rat, with maximal depletion of
5-HT in spinal cord and selected forebrain structures, and little effect in diencephalon and midbrain. Depletions in the guinea pig were less selective for
5-HT using
desipramine pretreatment than in the rat. In naive guinea pigs and rats, regional content of
5-HT was similar. These data suggest that the functional integrity of serotonergic neurons is not requisite for the expression of
myoclonus induced by
5-HTP in the guinea pig.
5,7-Dihydroxytryptamine lesions in the guinea pig resulted in behavioral and neurochemical similarities and differences in comparison with the rat.