Effects of acute and long-term treatment with methamphetamine on substance P concentration and receptor numbers in the rat brain.

To examine biochemical changes in brain substance P (SP) systems associated with development of behavioral sensitization induced by methamphetamine (MAP), regional substance P-like immunoreactivity (SP-LI) and SP receptor binding in the rat brain were measured after acute and long-term MAP administration. Single administration of 8 mg/kg MAP significantly reduced the striatal SP-LI concentration 1 h after the injection. This reduction was blocked by pretreatment with haloperidol. Although repeated administration of 4 mg/kg MAP for 14 consecutive days did not affect the SP-LI concentration in any brain regions including the striatum, it decreased specific SP receptor binding in the striatum and increased those in the frontal cortex. Scatchard analysis of saturation isotherm of specific SP binding revealed that the decreased specific SP binding in the striatum resulted from a decrease in the maximal number (Bmax) of SP receptors and that increased binding in the frontal cortex resulted from an increase in Bmax. These changes in SP receptor binding lasted for at least 7 days. It is emphasized that the persisting changes induced by long-term MAP administration in the SP receptor may contribute to behavioral sensitization to MAP in rats and may be associated with neuronal mechanisms in MAP psychosis.