Neurosciences
Program

Heiland, C.T., Hernandez, A.E., and Brady, A.M.  (2009, October).  An investigation of sex differences in behavior in the neonatal ventral hippocampal lesion rat model of schizophrenia.  Poster presented at the Society for Neuroscience Annual Meeting, Chicago, IL.

Abstract 

Patients with schizophrenia exhibit significant sex differences in the onset, symptomatology, treatment and prognosis of the disorder. Males typically have an earlier onset, more severe negative symptoms and cognitive deficits, less responsiveness to antipsychotic drugs, and a poorer prognosis. The present study compared female and male rats in the neonatal ventral hippocampal lesion (NVHL) model of schizophrenia. Rats received bilateral infusions of ibotenic acid (10 µg/µl; 0.3 µl; NVHL group) or artificial CSF (0.3 µl; sham group) into the ventral hippocampus at postnatal day (PD) 7. As adults (PD 56 or older), all animals completed three measures of behavior: prepulse inhibition (PPI), novelty-induced locomotion, and social interaction. Females were tested during proestrus and/or estrus phases of the estrous cycle, as determined by daily examination of vaginal cytology. PPI of the startle response was measured in acoustic startle chambers. As previously demonstrated, NVHL males (n = 8) showed a significant reduction in PPI compared to sham males (n = 6; p = .004). However, this impairment was not observed in females; NVHL females (n = 8) exhibited similar levels of PPI as sham females (n = 6; p = .389). To measure locomotion in a novel (stressful) environment, all animals were placed in automated activity chambers for 30 min and total ambulatory counts (beam breaks) were recorded. All animals decreased ambulation across time (p < .001), but there were no clear sex differences or effects of the NVHL. To measure social interaction, animals were paired with unfamiliar same-sex partners (at the same stage of the estrous cycle, for females) and were placed into the open field for 10 min. Social and nonsocial behaviors for each rat were scored from the videotaped interactions. Females engaged in more total social and nonsocial behavior than males (p = .003), and sham animals exhibited higher social and nonsocial behaviors than NVHL animals (p < .001). However, no interaction between sex and lesion was revealed. Together, these findings suggest that the NVHL manipulation can at least partially model the sex differences observed in the clinical manifestation of schizophrenia, particularly the more severe disruption of PPI in males.