Test-dependent variations in the antinociceptive effect of p-chloroamphetamine-induced release of 5-hydroxytryptamine.

p-Chloroamphetamine (PCA), in doses that did not significantly impair motor performance in a rotating-wheel task, induced marked analgesia in rats tested with the hot-plate and flinch-jump methods. In the tail-flick test, moderate hyper- or hypo-analgesia was found to be dependent on dose. In hot-plate experiments the analgesia was attenuated by inhibition of uptake of 5-HT (with zimelidine), depletion of stores of 5-HT (with PCPA) and by lesioning of 5-HT-containing terminals (long-term PCA treatment). Blockade of serotonin receptors by metergoline produced hyperalgesia, but failed to reduce the analgesia induced by p-chloroamphetamine. Manipulation of catecholaminergic and opioid systems did not reduce the effect of p-chloramphetamine. It is concluded that induction of release of 5-HT by chloroamphetamine induces antinociception which varies in magnitude between tests, suggesting that different serotonergic mechanisms modulate complex and reflex responses to noxious stimulation. The failure of metergoline to antagonize the analgesia induced by p-chloroamphetamine suggests an involvement of 5-HT receptors different from the ones implicated in other types of behaviour mediated by 5-HT.