Prenatal exposure to cocaine selectively disrupts the development of parvalbumin containing local circuit neurons in the medial prefrontal cortex of the rat.
Exposure to cocaine in utero can result in cognitive deficits potentially through a disruption in the inhibitory processes of the frontal cortex. One potential mechanism is through alterations in the inhibitory local circuit neurons containing the calcium-binding protein, parvalbumin. Parvalbumin-immunostaining primarily identifies 2 types of local circuit neurons: larger, rounder, axo-somal basket cells and smaller, more-spindle shaped, axo-axonic chandelier cells. Both are thought to have critical impact on the excitatory/inhibitory balance due to the proximal site of projection on pyramidal neurons. Calretinin, another calcium-binding protein, identifies a distinct sub-population of inhibitory local circuits that impinges more distally on the dendritic arbor and serves as a control population for this study. Here, we examine local circuit neurons containing either parvalbumin or calretinin in adolescent male rats (approximately 45 days old) exposed to saline or cocaine (3 mg/kg, intravenous twice a day during embryonic days 10 to 20). Prenatal cocaine exposure caused select changes in the parvalbumin, but not calretinin, containing cells in the frontal cortex. Specifically, prenatal cocaine exposure is associated with a 50% reduction in spindle-shaped parvalbumin-immunoreactive cells potentially indicating a select loss of chandelier cells or a shift to a rounder shape. Additionally, a reduction in the number of dendrites of parvalbumin-immunoreactive cells in rats exposed to cocaine in utero was noted. Other measures of both parvalbumin- and calretinin-immunoreactive cells were unchanged, including total number of cells, distribution by depth, and sizes of cells. These changes to the excitatory/inhibitory balance in the frontal cortex may contribute to the cognitive deficits associated with prenatal cocaine exposure.
Morrow
Bret A
BA
Neuropsychopharmacology Research Unit, Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8066, USA. bret.morrow@yale.edu
Elsworth
John D
JD
Roth
Robert H
RH
D000818:Animals; D002452:Cell Count; D048429:Cell Size / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D003712:Dendrites / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D005260:Female; D009415:Nerve Net / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010320:Parvalbumins / Q000032:analysis* / Q000502:physiology; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats
D010320:Parvalbumins; D003042:Cocaine