Neonatal ventral hippocampal lesions attenuate the nucleus accumbens dopamine response to stress: an electrochemical study in the adult rat.
Neonatal damage to the ventral hippocampus (VH) can lead, during adulthood, to behaviours that are believed to reflect enhanced mesocorticolimbic dopamine (DA) transmission. In the present study, the effects of neonatal excitotoxic lesions to the VH on spontaneous locomotor activity and stress-elicited increases in extracellular nucleus accumbens (NAcc) DA levels were examined in adult rats. Male pups received, on postnatal day 7, bilateral injections of either an ibotenic acid solution (lesioned) or vehicle (sham-lesioned) into the VH. At 3-4 months of age, animals were assessed during five daily sessions for changes in spontaneous locomotor activity associated with habituation to a novel environment. Voltammetry was used in separate groups of sham- and VH-lesioned animals to monitor the NAcc DA response to each of five once-daily exposures to tail-pinch stress. The results indicate that while VH-lesioned animals seem to habituate to novelty, they remain hyperactive relative to sham-lesioned controls. In contrast, however, stress consistently elicited in VH-lesioned animals smaller and shorter-lasting increases in NAcc DA than in sham-lesioned controls. These data suggest that neonatal excitotoxic damage to VH leads to changes in DA function that persist into adulthood. The blunted response to stress seen in VH-lesioned animals indicates that one consequence of such damage is a functional hyporeactivity in meso-NAcc DA neurons. The fact that these animals are spontaneously more active suggests compensatory changes in DA function that are efferent to DA terminals in NAcc.
Douglas Hospital Research Centre, McGill University, Department of Psychiatry, 6875 LaSalle Blvd., Verdun, Quebec, Canada.
W G
WG
Brake
R M
RM
Sullivan
G
G
Flores
L K
LK
Srivastava
A
A
Gratton
D000818:Animals; D000831:Animals, Newborn; D004298:Dopamine / Q000502:physiology*; D004563:Electrochemistry; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology*
D004298:Dopamine