Prenatal haloperidol reduces the number of active midbrain dopamine neurons in rat offspring.
The dopamine (DA) receptor antagonist, haloperidol (HAL, 1.25 or 5 mg/kg), or vehicle, dimethyl sulfoxide (DMSO), was administered (SC) daily to pregnant Sprague-Dawley dams from gestational day (GD) 8 to GD 20. The average body weight of 2-week-old male offspring was significantly lower in all of the HAL-treated groups relative to controls. In extracellular electrophysiological studies, the male 2-week-old offspring from all HAL treatment groups were found to have significantly reduced average numbers of spontaneously active midbrain dopamine (DA)-containing neurons in both the substantia nigra (A9) and the ventral tegmental area (A10) relative to controls. In DA neurons classified as bursting neurons, HAL exposure (5 mg/kg) caused a significantly increased level of burst activity in A10 but not A9 DA neurons relative to controls. For both the A9 and A10 regions, the proportion of DA neurons classified as bursting or nonbursting was unaffected by HAL treatment. These results suggest that prenatal HAL exposure influences the development of midbrain DA neurons.
Zhang
J
J
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, MI 48202, USA.
Wang
L
L
Pitts
D K
DK
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D003864:Depression, Chemical; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000633:toxicity*; D004594:Electrophysiology; D005260:Female; D006220:Haloperidol / Q000633:toxicity*; D007279:Injections, Subcutaneous; D008297:Male; D008636:Mesencephalon / Q000166:cytology* / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D018492:Dopamine Antagonists; D006220:Haloperidol; D004298:Dopamine