Inhibitory effects of newly synthesized Ser-contained GABA-peptides administered into either caudate putamen or amygdala on methamphetamine-induced hyperactivity.

The locomotor activities induced by methamphetamine (MAP: 1 mg/kg) following the microinjection of either GABA or three synthesized GABA-peptides (PLG, PSLG, PDSLG) into the rat caudate putamen or the amygdala were measured by using behavioral analysis. The ip administration of MAP induced hyperactivities in a time-dependent manner, and the maximum activity was measured 30 min after MAP administration. This hyperactivity was observed for more than 2 hrs. By the microinjection of GABA-peptides (0.054-540 nmol) into each brain region, the MAP-induced hyperactivity was significantly reduced in a dose-dependent manner, although the single administration of examined dosages of these peptides did not influence the locomotor activity. In the case of microinjection of GABA into either one of the brain regions, only the larger dosage (27,000 nmol) significantly reduced the MAP-induced hyperactivity, whereas this inhibition was less than that seen at the dose of 540 nmol of GABA-peptides. Furthermore, the microinjection of newly synthesized GABA-peptides, PSLG and PDSLG, into the caudate putamen was more effective than those obtained by injection into the amygdala. However, either microinjection of PLG or GABA into both regions showed similar inhibition. These results suggest that the pharmacological properties of newly synthesized GABA-peptides are different compared to those of PLG and GABA, and that these differences might be due to the primary inhibitory effects of the serine-contained GABA-peptides on dopaminergic neuronal activity, but not on GABA neurons.