The lateral habenula is a nucleus in the dorsal thalamus that innervates mi
dbrain dopaminergic and serotonergic nuclei via projections through its maj
or efferent pathway, the fasciculus retroflexus (FR). It was previously dem
onstrated that cocaine administered continuously to adult rats over several
days produces neurodegeneration in the lateral habenula and FR. Because ex
posure to cocaine during pregnancy reportedly can cause neurobehavioral def
icits, we examined whether rat fetuses exposed to continuous cocaine during
the last week of gestation would similarly demonstrate selective neurodege
neration in the lateral habenula. On day 17 of gestation, dams were implant
ed with two silicone pellets, each containing either vehicle or one of 2 do
ses of cocaine (80 mg or 55 mg per pellet). Degenerating neurons containing
silver deposits were counted in lateral habenula and in the striatum. Coca
ine-exposed pups had significantly more silver-stained cells in the lateral
habenula than vehicle-treated pups, but similar numbers of silver-stained
cells were present in the striatum of all three groups. When similarly trea
ted vehicle- and cocaine-exposed animals were tested behaviorally at 60 day
s of age, they did not differ on measures of open field activity, open arm
avoidance on the elevated plus-maze or conditioned place preference for coc
aine, although a linear trend analysis indicated some hyperactivity of the
cocaine-pretreated pups during the place preference test. These results ind
icate that continuous cocaine exposure has selective neurotoxic effects on
the habenula of the developing fetus similar to cocaine's effects in the ad
ult. (C) 1999 Elsevier Science B.V. All rights reserved.