| Summary: | A rat model was used to determine whether prenatal cocaine exposure results in long-term changes in hippocampal-dependent contextual fear conditioning. Pregnant dams received either 40 mg/kg cocaine HCl SC (COC), an equal volume of 0.9% saline (SAL), or received no injections (UT) from gestational day 8 through 20. SAL animals were also pair-fed to COC subjects. Experiment 1 tested one-trial contextual fear conditioning in adult male offspring. Freezing and defecation were measures of fear. Prenatal cocaine exposure did not affect context conditioning, but there was an overall increase in SAL and COC defecation, indicating an increased generalized fear in these subjects. To better mimic binge cocaine use, COC dams in Experiment 2 and 3 received 20 mg/kg cocaine HCl SC, b.i.d. A preliminary open field task revealed that SAL offspring were more exploratory than UT controls and that females were more active than males. In Experiment 2, adult male and female offspring received 4 days of context conditioning and 3 days of no-shock extinction. During extinction, access to an adjacent chamber enabled the observation of four additional measures of fear: side crossing, latency, nose crossing, and side-differential. Experiment 2 repeated previous reports of gender-specific contextual fear. Males showed a greater level of freezing and defecation, higher latencies and side-differentials, and a lower level of side crossings and nose crossings than females. Prenatal cocaine exposure resulted in exaggerated gender-specific fear conditioning as measured by nose-crossing and side differential during extinction. Experiment 3 tested the effects of prenatal cocaine exposure on latent inhibition (LI) of contextual fear in year-old females. Vertical nose crossing (VNC), freezing, and defecation were measures of fear. LI was evidenced as an attenuation of freezing and VNC in pre-exposed (PE) animals compared to non-pre-exposed subjects. Prenatal cocaine exposure resulted in an enhanced LI effect. COC females showed a low level of baseline VNC, but COC-PE subjects showed a greater level of VNC than controls following the first shock during conditioning. The results of these experiments suggest that the effects of prenatal cocaine exposure on hippocampal-dependent learning are subtle, selective, and gender specific.
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