Effect of amphetamine, cocaine and depolarization by high potassium on extracellular dopamine in the nucleus accumbens shell of SHR rats. An in vivo microdyalisis study.
Spontaneously hypertensive rats (SHR) exhibit behavioural abnormalities (hyperactivity and hyper reactivity to stress) that resemble the behavioural abnormalities of human attention-deficit with hyperactivity disorder (ADHD). Because dopamine has been implicated in ADHD we studied by in vivo microdialysis the dopamine output in the nucleus accumbens (NAc) shell of 6 week-old (pre-hypertensive stage) SHR rats and in their normotensive age matched Wistar Kyoto controls (WKY). We observed that SHR rats had significant higher basal dialysate dopamine concentrations (about 20%) than WKY. Systemic administration of amphetamine (0.25 and 0.5 mg/kg s.c.), and methylphenidate (1 and 2 mg/kg i.p.) produced an higher increase in dialysate dopamine in the NAc shell of SHR rats as compared with WKY rats, although only after the administration of the lowest dose of amphetamine and methylphenidate this difference was found to be significant. In contrast when the microdialysis fiber was perfused by 30 or 60 mM K(+), a lower increase of dialysate dopamine was observed in SHR rats as compared with WKY rats. These apparently contradictory results can be explained by postulating that SHR rats have a higher tone of NAc shell dopamine transmission and synthesis associated with a lower storage capacity of vesicles in dopamine terminals of the same area.
Carboni
Ezio
E
Department of Toxicology, Centro di Eccellenza sulla Neurobiologia delle Dipendenze, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy. ecarboni@unica.it
Silvagni
Alessandra
A
Valentini
Valentina
V
Di Chiara
Gaetano
G
D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000737:chemistry; D008297:Male; D016555:Matched-Pair Analysis; D008564:Membrane Potentials / Q000187:drug effects; D008774:Methylphenidate / Q000494:pharmacology*; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D018765:Dopamine Uptake Inhibitors; D008774:Methylphenidate; D000661:Amphetamine; D003042:Cocaine; D011188:Potassium; D004298:Dopamine