Involvement of serotonergic and dopaminergic mechanisms in hyperthermia induced by a serotonin-releasing drug, p-chloroamphetamine in mice.

Serotonergic and dopaminergic involvement in hyperthermia induced by a serotonin (5-hydroxytryptamine, 5-HT)-releasing drug, p-chloroamphetamine, was investigated in mice. Neither the 5-HT transporter inhibitor fluoxetine nor the 5-HT depleter p-chlorophenylalanine affected p-chloroamphetamine-induced hyperthermia. The dopamine depleter -methyl-p-tyrosine significantly reduced p-chloroamphetamine-induced hyperthermia. The dopamine D₁ receptor antagonist 7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390) antagonized p-chloroamphetamine-induced hyperthermia, although the dopamine D₂ receptor antagonist sulpiride was without effect. These results indicate that p-chloroamphetamine-induced hyperthermia in mice is mediated by dopamine release followed by activation of the dopamine D₁ receptor.