DECLINES IN STIMULATED STRIATAL DOPAMINE RELEASE OVER THE FIRST 32 H FOLLOWING MICRODIALYSIS PROBE INSERTION - GENERALIZATION ACROSS RELEASING MECHANISMS

In a recent paper [R.R. Holson, J.F. Bowyer, P. Clausing, B. Gough, Me thamphetamine-stimulated striatal dopamine release declines rapidly ov er time following microdialysis probe insertion, Brain Res. 739 (1996) 301-307] we reported that methamphetamine-stimulated striatal dopamin e release declined rapidly over the first eight hours following microd ialysis probe insertion. This decline was strictly a function of time post-probe implantation, and not due to tolerance or desensitization. To further examine this phenomenon, we subjected rats to three brief p ulses of several DA-releasing compounds at 2, 4 and 6 h post-probe ins ertion, and compared these results to those caused by a single pulse 6 h post-insertion, or in some cases to pulses given more than 24 h pos t-insertion. We found that when buproprion, a dopamine reuptake blocke r, was infused briefly into the striatum via the microdialysis probe, there was a pronounced drop in the amount of dopamine released at 6 h vs. 2 h post insertion; this drop was not due to repeated exposure, si nce dopamine release at 6 h post-insertion was the same for a single p ulse, or when preceded by two earlier pulses. Twenty-four hours later, buproprion-stimulated dopamine release was still lower, but did not a ppear to drop further thereafter. Potassium-stimulated dopamine releas e, on the other hand, dropped rapidly over the first 8 h post-insertio n, and this decline continued throughout the 24-32 h interval post-ins ertion. Similarly, a single i.p. injection of 0.5 mg/kg haloperidol re leased three times as much dopamine when given two compared to six hou rs post-implantation. Both bupropion- and potassium-stimulated dopamin e release were accompanied by declines in extracellular DOPAC concentr ations, and these declines were the same 2 or 26 h post-insertion. In contrast, haloperidol exposure increased extracellular DOPAC, and this haloperidol-stimulated DOPAC increase was also greatly attenuated at 6 compared to 2 h post-insertion. We conclude that there is a general decline over time post-probe implantation in the ability of the striat al dopamine system to release dopamine, and perhaps to increase dopami ne synthesis, in response to pharmacological challenges. (C) 1998 Else vier Science B.V. All rights reserved.