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, Methamphetamine-stimulated striatal dopamine release declines rapidly over time following microdialysis probe insertion, Brain Res. 739 (1996) 301-307] we reported that methamphetamine-stimulated striatal dopamine release declined rapidly over the first eight hours following microdialysis 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 pulses of several DA-releasing compounds at 2, 4 and 6 h post-probe insertion, 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 post-insertion. We found that when buproprion, a dopamine reuptake blocker, 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, since dopamine release at 6 h post-insertion was the same for a single pulse, or when preceded by two earlier pulses. Twenty-four hours later, buproprion-stimulated dopamine release was still lower, but did not appear to drop further thereafter. Potassium-stimulated dopamine release, on the other hand, dropped rapidly over the first 8 h post-insertion, and this decline continued throughout the 24-32 h interval post-insertion. Similarly, a single i.p. injection of 0.5 mg/kg haloperidol released three times as much dopamine when given two compared to six hours post-implantation. Both bupropion- and potassium-stimulated dopamine release were accompanied by declines in extracellular DOPAC concentrations, 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 striatal dopamine system to release dopamine, and perhaps to increase dopamine synthesis, in response to pharmacological challenges.
Holson
R R
RR
Department of Psychology, New Mexico Tech, Socorro, NM 87801, USA. rholson@nmt.edu
Gazzara
R A
RA
Gough
B
B
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D019771:Axotomy; D016642:Bupropion / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D016642:Bupropion; D015102:3,4-Dihydroxyphenylacetic Acid; D006220:Haloperidol; D011188:Potassium; D004298:Dopamine