This Is AuburnElectronic Theses and Dissertations

Elucidation of the mechanism of learning and memory deficits in adolescent offspring due to prenatal cannabinoid exposure




Pinky, Priyanka

Type of Degree

PhD Dissertation


Interdepartmental Pharmacy

Restriction Status


Restriction Type

Auburn University Users

Date Available



Cannabis is now one of the most commonly used illicit substances among pregnant and lactating women. This is particularly concerning given that developmental exposure to cannabinoids has been demonstrated to induce enduring neurofunctional and cognitive alterations in clinical studies, yet there is a relative paucity of preclinical literature investigating the underlying neurocognitive alterations resulting from prenatal exposure to cannabinoids. In the current study, we provide a mechanistic evidence on how learning and memory deficits result from prenatal cannabinoid exposure (PCE) in adolescent offspring. We have investigated the effect of PCE on hippocampal and cerebellar function in a pregnant rodent model. PCE induced deficits in hippocampal-dependent memory tasks in adolescent offspring, and these behavioral deficits were associated with decreased long-term potentiation (LTP) and enhanced long-term depression (LTD) at hippocampal Schaffer collateral-CA1 synapses, as well as an imbalance between GluN2A- and GluN2B- mediated signaling. Moreover, PCE reduced gene and protein expression of neural cell adhesion molecule (NCAM) and polysialylated-NCAM (PSA-NCAM), which is critical for GluN2A and GluN2B signaling balance. Restoration of PSA-NCAM activity restored the LTP deficits observed in PCE animals, suggesting PSA-NCAM mediated alterations in GluN2A- and GluN2B- signaling pathways are responsible for the altered synaptic plasticity in hippocampus resulting from PCE. Interestingly, PCE has shown to exert an anti-apoptotic effect on the cerebellum by decreasing oxidative stress markers and nitrite content. Our study indicates that effects of PCE on the cerebellum are unique compared to other brain regions by enhancing mitochondrial complex I and complex IV function to promote neuronal survival and reducing the level of pro-apoptotic factor caspase 3 and apoptosis associated signaling. These findings enhance the current understanding of how PCE affects cognition and neuronal survival, and how this process can be manipulated for future therapeutic purposes.