Involvement of 5-HT1A receptor mechanisms in the inhibitory effects of methamphetamine on photic responses in the rodent suprachiasmatic nucleus

We examined the role of serotonin 1A (5-HT1A) receptors in the inhibitory effects of methamphetamine (MA) on photic entrainment to the circadian pacemaker in the suprachiasmatic nucleus (SCN) of rodents. MA inhibited optic nerve stimulation-evoked field potential in the SCN, light-induced Fos expression in the SCN and light-induced phase shift of hamster wheel-running rhythm. NAN-190, a 5-HT1A receptor antagonist, eliminated the inhibitory effects of MA. NAN-190 has also been reported to antagonize alpha 1 adrenergic receptors. However, prazosin, which selectively antagonizes alpha 1 adrenergic receptors, did not affect the inhibitory action of MA on light-induced Fos expression. In addition, parachloroamphetamine, which is known to be a 5-HT releaser, dose-dependently inhibited light-induced phase shift of wheel-running rhythm. These findings suggest that elevation of endogenous 5-HT levels by MA inhibits the photic entraining responses of the circadian pacemaker in the SCN via 5-HT1A receptor stimulation of the 5-HT released by MA.