Developmental differences in acute nigrostriatal and mesocorticolimbic system response to haloperidol.
Dose-dependent effects of haloperidol (2.66 nmol/kg to 79.8 mmol/kg, IP) on levels of dopamine, homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) were assessed in the corpus striatum, nucleus accumbens, and medial prefrontal cortex (PFCTX) of 18-, 30-, and 110-day-old rats. Eighteen-day-old rats were 35% and 63% more sensitive than adults to the effects of haloperidol on striatal and accumbens turnover and had steeper dose-response curves. The dose-response function in the PFCTX was similar to striatum at 18 days, but became shallower and nonsigmoidal with age. Maximally effective doses of haloperidol produced, at all ages, a comparable percent rise in DOPAC levels in all regions. With maturation, the percent rise in HVA progressively outstripped DOPAC response in nucleus accumbens and striatum. Overall, prominent developmental differences emerged in these regions in their sensitivity and response to haloperidol, which are consistent with previously reported differences in behavioral sensitivity.
Teicher
M H
MH
Department of Psychiatry, McLean Hospital, Belmont, MA 02178.
Barber
N I
NI
Gelbard
H A
HA
Gallitano
A L
AL
Campbell
A
A
Marsh
E
E
Baldessarini
R J
RJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D004298:Dopamine / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008032:Limbic System / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism
D015102:3,4-Dihydroxyphenylacetic Acid; D006220:Haloperidol; D004298:Dopamine; D006719:Homovanillic Acid