Cocaine-induced dopamine overflow within the nucleus accumbens measured by in vivo microdialysis: a meta-analysis.
A meta-analysis was conducted on data obtained from published articles which used in vivo microdialysis to assess dose-response curves of cocaine on dopamine (DA) overflow within the nucleus accumbens (NAC). Different experimental and biological parameters such as route of administration (ip, sc, iv, local), rat and mouse strains, gender, age aspects, and regions cannulated (NAC core and shell) were considered. Data from 116 experiments involving 833 animals (out of 266 publications) fulfilled our selection criteria and were analyzed in relation to absolute basal DA levels, the maximum peak of DA overflow (peak [%] baseline) and the time when this peak (peak time) occurred. Our meta-analysis revealed that absolute basal DA levels lie at 2.39 nM (median of all experiments) and that cocaine-induced DA overflow in the NAC is significantly enhanced in a linear dose-response fashion within the applied dose range as the regression function increases following either iv or ip administration. Peak time was reached fastest in iv experiments and slowest following local application. Furthermore, it was shown in ip experiments that the higher the dose, the longer it took to reach the zenith. Results from the NAC shell region displayed greater DA overflow as compared with the NAC core. DA overflow properties following cocaine treatment in mice did not differ from that in rats. Thus, neither species differences nor other biological factors such as, age, gender, and rat/mouse strain have a pronounced impact on cocaine-induced DA overflow. Technical parameters of the microdialysis procedure such as calcium concentration of the perfusion medium and collected sample amount have also no significant effect in terms of DA overflow properties (peak [%] baseline and peak time) following cocaine treatment. In conclusion, these data may be deemed useful for textbook knowledge and a better comparability of data given by the generalization of already existing data as well as for investigators in maximizing the effect of cocaine-induced DA overflow. Finally, this study examplifies how meta- analyses may be applied to a wide range of data within the field of neurochemistry.
Frank
Stefanie Th
ST
Department of Psychopharmacology, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
Krumm
Bertram
B
Spanagel
Rainer
R
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D051379:Mice; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D004298:Dopamine