A single dose of mianserin (I) [24219-97-4] (2 mg/kg) given to rats 24, 48, and 72 h before L-5-hydroxytryptophan Et ester HCl (II) administration (12.5 mg/kg, i.v.) did not affect the number of II-induced shakes, whereas a 4 day administration increased the number of shakes 48 and 72 h after withdrawal, and a 10 day treatment reduced and increased the number of shakes 48 and 72 h resp. after withdrawal.A single dose of danitracen (III) [31232-26-5] (3 mg/kg) 72 h before II increased by ∼50% the number of shakes, and a greater increase occurred after 72 h with 4- and 10-day treatments, whereas there was a reduction after 24 h withdrawal.A single dose of amitriptyline [50-48-6] (10 mg/kg) 72 h before II had no effect, whereas 4- and 10-day treatments increased the number of shakes.Thus, a prolonged blockade of 5-hydroxytryptamine (5-HT) receptors by I and III enhanced the shake response to II.The lack of an enhanced response to II in the initial period, and the reduced response, may have been due to a permanent presence of the drug blocking 5-HT receptors.In addition to its effect on 5-HT uptake, amitriptyline may also block 5-HT postsynaptic receptors.