tested during drug administration and during drug abstinence. THCaltered activity, anxiety, and cocaine reward differently in male andfemale rats. Possible mechanisms for these sex differences will alsobe presented. In summary, the role of endocannabinoids in braindevelopment and the effects of THC administration during theprenatal or adolescent period will be presented. THC produceslong-term effects on cognition, affect, and drug reward. Therefore,smoking marijuana during pregnancy or adolescence has long-termeffects on brain function. (Supported by NIH grants DA 019348 andP50 DA 025484-0001)

doi:10.1016/j.ntt.2012.05.016

NBTS 16Developmental cannabis exposure and its epigenetic consequences

Yasmin HurdMount Sinai School of Medicine, New York, NY, United States

Marijuana (Cannabis sativa) continues to be the most used illicit drugin theUSAwith recentyears showingadisconcerting increaseduseamongteens and reduced perceived risk of harm associated with the use of thisdrug. Such perception also fuels the debates as to whether there are anysignificant developmental effects of cannabis exposure. To address thesequestions and to obtain insights into the potential relationship ofdevelopmental cannabis exposure to psychiatric vulnerability, we havestudied molecular mechanisms in the brains of human subjects with inutero cannabis exposure, as well as animal models in which drug historycould be controlled and causal effects on behavior could be betterestablished. Our results have revealed specific long-term molecular dis-turbances of prenatal and adolescent cannabis/D9-tetrahydrocannabinol(THC; psychoactive component of cannabis) exposure of genes associatedwith mesolimbic striatopallidal circuit (e.g., proenkephalin and D2). Thefact that these striatopallidal genes are critical to reward and impulsivitysuggests the potential of early cannabis exposure to disturb neurobiolo-gical systems significantly associated with addiction vulnerability in linewith altered heroin self-administration behavior seen in our develop-mental THC rodent models. Moreover, our studies have begun tocharacterize specific THC-induced epigenetic histone modifications thatappear to maintain the protracted discrete gene expression disturbancesafter exposure to the drug. In addition, new experiments have begun toreveal cross-generational effects associated with adolescent THC expo-sure. Overall, these and other ongoing studies emphasize the significantcontribution of developmental cannabis to epigenetic disturbances thatmay relate to psychiatric vulnerability.

doi:10.1016/j.ntt.2012.05.017

NBTS 17Endocannabinoid-CB1R signaling: A link between early life stressand changes in limbic system function?

Cecilia Hillard, Dylan CossMedical College of Wisconsin, Milwaukee, WI, United States

Considerable evidence has accumulated suggesting that endogenousCB1R signaling (ECS) is stress responsive. Recent studies in hypothala-mus, hippocampus and prefrontal cortex demonstrate that glucocorti-coids mobilize ECS. Endocrine and behavioral effects of stress are alteredby ECS. For example, ECS in the medial prefrontal cortex is required forappropriate recovery of the hypothalamic–pituitary–adrenal axis follow-ing stress and inhibition of ECS potentiates anxiety-like behaviors inseveral models. ECS exhibits plasticity; it is down-regulated in several

models of chronic stress. Taken together, considerable experimentalevidence supports the hypotheses that ECS functions as a stress buffer inthe brain and can be modified by previous experience. Humanepidemiological and preclinical evidence demonstrate that exposure tostress in early life results in life-long alterations in behavioral andendocrine responses to stress. Therefore, we hypothesized that stress inearly life results in long-lasting alterations in ECS that contribute tochanges in endocrine and behavioral responses to stress exposure in laterlife. Sprague Dawley dams and litters were exposed to limited beddingstress using the model of Baram and colleagues. From days 1–9 of age,bedding was reduced to one-third of normal (0.5 liters in a standard ratcage) in the stress cohort. Pupswere sacrificedonday10 andCB1RmRNAwasquantified inprefrontal cortex (PFC) andamygdalausingqPCR. In thePFC, significant main effects of both sex and stress exposure, as well as asignificant interaction, occurred. Post hoc tests revealed that female pupshad significantly greater CB1R mRNA expression than males. Stressexposure significantly reduced mRNA expression in both sexes; theeffect was greater in females (75% reduction) than males. In amygdala,significant main effects of both sex and stress exposure were observed;post hoc tests revealed that stress produced a significant reduction inCB1RmRNA expression only in females. These data suggest that early lifestress alters the expression of the CB1R in brain regions critical for stressresponsivity in a sex-specific manner and support the hypothesis thatearly life stress can modulate ECS, particularly in female offspring.

doi:10.1016/j.ntt.2012.05.018

NBTS 18Developmental effects of marijuana exposure: Gestation andearly adolescence

Nancy L. DayUniversity of Pittsburgh School of Medicine, Pittsburgh, PA, United States

There are two points in human development that are known to becritical times for marijuana exposure. The first, exposure duringgestation, has been shown to have long-term effects on thedevelopment of the offspring. These are CNS deficits expressed asbehavioral and cognitive problems. There have been few reports ofprenatal marijuana exposure (PME) affecting growth or morphology.The second vulnerable period is during early adolescence. Adoles-cents who begin to use marijuana before age 16, defined as early ageof onset (EAO), have more behavioral problems, and a higher rate ofmental disorders, including the development of psychotic symptomsand psychotic disorders. It has also been shown that PME predicts theage of onset of marijuana use. This presentation will use the findingsfrom the Maternal Health Practices and Child Development Study,which is a longitudinal study of the long-term effects of PME. In thisstudy, mothers were recruited during their fourth prenatal monthand the mothers and offspring have been followed through theoffspring age of 22 years. The cohort size at birth was 519 mother/child pairs. This presentation will discuss these two critical exposureperiods and the effects of exposure to PME and EAO on subsequentbehaviors and psychiatric symptomatology and disorders.

doi:10.1016/j.ntt.2012.05.019

NBTS 19Illicit and prescription drugs targeting the developingserotonergic system have deleterious effects on cognition

Tori Schaefera, Curtis Graceb, Devon Grahamc, Matthew Skeltona,Michael Williamsa, Charles Vorheesa

NBTS 2012 Abstracts 373