Prenatal immune challenge in rats: Altered responses to dopaminergic and glutamatergic agents, prepulse inhibition of acoustic startle, and reduced route-based learning as a function of maternal body weight gain after prenatal exposure to poly IC

Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, Ohio 45229, USA.
Synapse (Impact Factor: 2.13). 08/2012; 66(8):725-37. DOI: 10.1002/syn.21561
Source: PubMed


Prenatal maternal immune activation has been used to test the neurodevelopmental hypothesis of schizophrenia. Most of the data are in mouse models; far less is available for rats. We previously showed that maternal weight change in response to the immune activator polyinosinic-polycytidylic acid (Poly IC) in rats differentially affects offspring. Therefore, we treated gravid Harlan Sprague-Dawley rats i.p. on embryonic day 14 with 8 mg/kg of Poly IC or Saline. The Poly IC group was divided into those that lost or gained the least weight, Poly IC (L), versus those that gained the most weight, Poly IC (H), following treatment. The study design controlled for litter size, litter sampling, sex distribution, and test experience. We found no effects of Poly IC on elevated zero maze, open-field activity, object burying, light-dark test, straight channel swimming, Morris water maze spatial acquisition, reversal, or shift navigation or spatial working or reference memory, or conditioned contextual or cued fear or latent inhibition. The Poly IC (H) group showed a significant decrease in the rate of route-based learning when visible cues were unavailable in the Cincinnati water maze and reduced prepulse inhibition of acoustic startle in females, but not males. The Poly IC (L) group exhibited altered responses to acute pharmacological challenges: exaggerated hyperactivity in response to (+)-amphetamine and an attenuated hyperactivity in response to MK-801. This model did not exhibit the cognitive, or latent inhibition deficits reported in Poly IC-treated rats but showed changes in response to drugs acting on neurotransmitter systems implicated in the pathophysiology of schizophrenia (dopaminergic hyperfunction and glutamatergic hypofunction).

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    • "Animals tested for locomotor activity received three phases of testing: Baseline with no treatment; Saline with saline-only injection; and drug challenge with one of three drugs (see [29] [69] [70]). At young ages, there was no significant main effect of diet; there was a significant diet × interval interaction (F(11,3466) = 2.39, p < 0.01). "
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    • "The present results using Long Evans rats are consistent with previous reports that MIA during pregnancy does not alter classical fear conditioning in the adult male offspring of either Wistar (Zuckerman and Weiner, 2005) or Sprague Dawley rat strains (Vorhees et al., 2012; Yee et al., 2012). The previous studies assessed freezing to auditory cues and context previously paired with footshock (Vorhees et al., 2012; Yee et al., 2012) and suppression of licking to an auditory cue previously paired with footshock in a conditioned emotional response paradigm (Zuckerman and Weiner, 2005). We report robust freezing to the cue and context on day one during conditioning and day 2 during the initial phase of the first extinction session, which provides a measure of conditioning recall 24 h after training (Figure 2). "
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