Dopamine responsiveness to drugs of abuse: A shell-core investigation in the nucleus accumbens of the mouse.
The existence of subterritories within the nucleus accumbens has now been widely supported by histochemical, neurochemical, electrophysiological, as well as morphological and ultrastructural studies and suggest specific afferent and efferent systems involved in different behavioral aspects. Microdialysis studies in the rat have consistently shown that most drugs of abuse increase extracellular dopamine levels preferentially in the shell subregion of the nucleus accumbens. The study of the relative roles of NAc subregions may considerably help our understanding of the neurobiological basis of drug addiction. Accordingly, the aim of the present work was to extend the outcome of rat studies to the mouse species. Five major drugs of abuse were systemically and acutely administered to mice with a microdialysis probe implanted in either the shell or the core. A statistical comparison was performed on data transformed as percentage values of baseline dopamine vs. logarithmic values with baseline dopamine as a covariate. Results show a significant increase in dopamine levels in both the shell and core subregions following cocaine, amphetamine, nicotine, ethanol, and morphine treatments. A difference between shell and core after cocaine, nicotine, and morphine was evident when data were analyzed as percent values of baseline. However, such a shell-core dichotomy became no longer significant when ANOVA was applied on the statistically more appropriate logarithmic transformation of data with baseline as a covariate. The significant baseline differences among groups of mice (dopamine levels in the shell significantly lower compared with dopamine levels in the core) may have compromised, at least in part, the statistical procedure usually applied in microdialysis studies. These findings suggest that a careful evaluation of the data is required when subtle changes in extracellular levels of DA are measured.
Zocchi
Alessandro
A
Centre of Excellence for Drug Discovery in Psychiatry, GlaxoSmithKline Pharmaceuticals, 37135 Verona, Italy. alessandro.a.zocchi@gsk.com
Girlanda
Elena
E
Varnier
Giorgia
G
Sartori
Ilaria
I
Zanetti
Lara
L
Wildish
Grant A
GA
Lennon
Mark
M
Mugnaini
Manolo
M
Heidbreder
Christian A
CA
D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D064026:Calbindins; D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D013287:Illicit Drugs / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D017551:Microdialysis / Q000379:methods; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D019966:Substance-Related Disorders / Q000378:metabolism*; D013997:Time Factors
D000779:Anesthetics, Local; D064026:Calbindins; D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D013287:Illicit Drugs; D009294:Narcotics; D018722:Nicotinic Agonists; D064030:S100 Calcium Binding Protein G; D000431:Ethanol; D009538:Nicotine; D009020:Morphine; D000661:Amphetamine; D003042:Cocaine; D004298:Dopamine