METHAMPHETAMINE-STIMULATED STRIATAL DOPAMINE RELEASE DECLINES RAPIDLYOVER TIME FOLLOWING MICRODIALYSIS PROBE INSERTION

To investigate changes in striatal dopamine release over a series of b rief methamphetamine (METH) exposures, METH was pulsed three times at 2-h intervals, with the first exposure occurring 2 h after microdialys is probe insertion. Whether METH was administered directly into the st riatum via the microdialysate (20 mu M Of METH for 10 min), or via per ipheral intraperitoneal (i.p.) injection (1 mg/kg METH, i.p.), the dop amine (DA) peak elicited by the third METH exposure was only 50% as la rge as that elicited by the first exposure, 4 h earlier. This decline in the magnitude of METH-induced DA release probably continued over at least 24 h, since the magnitude of a single peak 26 h after probe imp lantation was only one-seventh of that at 2 h. This reduction in the r esponse to METH was a function of time post-probe insertion, and not o f prior METH exposure. Thus, peak size was the same at 6 h post-implan tation in animals which received two prior METH pulses or no prior MET H pulses, and in both cases this 6-h peak was substantially lower than that at 2 h post-implantation. Circadian influences were also exclude d as a factor, because size of the initial METH-induced DA peak did no t vary as a function of time of probe implantation. It is concluded th at METH-stimulated striatal DA release declines rapidly over time post -probe insertion. When METH exposures occur repeatedly at short interv als, this decline can mimic, but is not caused by, desensitization or depletion in response to prior METH exposure.