Effects of Chronic Adolescent Cannabinoid Exposure on Decision-Making Under Uncertainty in Adulthood

Adolescence is characterized by increases in risk-taking across a range of behaviors, including experimentation with alcohol and illicit drugs. Cannabis is the most widely used illicit drug among adolescents, and increased use coincides with a period of marked brain development, particularly in the prefrontal cortex (PFC). PFC is important for decision-making processes, and exposure to cannabis during PFC development may lead to impairments in these processes, resulting in increased impulsivity and excessive risk-taking. The medial portion of prefrontal cortex (mPFC), continues to develop throughout adolescence, and is thought to be crucial is shifting behavior as rewards become uncertain or less valuable. In this study, we investigated the long-term effects of chronic adolescent cannabinoid exposure on risk deicison-making. 32 male and female Long Evans rats received i.p. injections of WIN 55, 212-2, a CB1 agonist, from postnatal day 30-60. Once animals reached adulthood, their risk-preference was measured using a gambling task. Rats chose between two levers, one of which paid a small, certain reward, and the other paid a larger, probabilistic reward. The probability of receiving the large reward varied randomly on each session, ranging from 16.7% to 66.7%. As rats performed this task, we used in vivo electrophysiology to record mPFC activity. Neural responses to cues and outcomes are compared across the range of probabilities between WIN-treated animals and controls

Understanding Mechanisms of Vulnerability During Adolescence: A Role for Perineuronal Nets

A hallmark of adolescent brain development is the establishment of a finely-tuned excitatory-inhibitory (E-I) balance in the prefrontal cortex (PFC). This balance, which comes online as inhibitory signaling is refined, helps regulate neuron activity and is essential for the acquisition of higher cognitive function, such as decision-making, in adulthood. It is widely accepted that the maturation of parvalbumin-containing (PV+) interneurons is critical for developing E-I balance, as PV+ interneurons are known to regulate excitability of other cells. Interestingly, approximately 70% of PV+ interneurons in PFC are surrounded by perineuronal nets (PNNs), a lattice-like structure that forms around them during critical periods of development and regulates their plasticity. Drugs of abuse are known to affect PNNs in adulthood, but few researchers have studied the impact of drug use on PNNs during development. Cannabis, the most commonly used illicit drug among adolescents, is known to alter E-I balance by disrupting the development of PV+ cells, so we began by investigating whether cannabis might be exerting its effects by disrupting PNN development and making PV+ cells vulnerable to insult. Addiitionally, this work explored whether disruptions in PFC PNNs would lead to functional deficits in decision-making, a PFC dependent behavior. If this is the case, then PNNs may be one neurobiological mechanism that underlies the effects of cannabis on the developing brain. Enhancing our understanding of both the immediate and lasting effects of cannabinoids on the developing brain will elucidate the consequences of substance use during adolescence, with implications for the study of addiction and adolescent-onset psychiatric disorders, as well as cannabis policy

Mapping preictal networks preceding childhood absence seizures using magnetoencephalography

The electrographic hallmark of childhood absence seizures is 3 Hz generalized spike and wave discharges; however, there is likely a focal thalamic or cortical onset that cannot be detected using scalp electroencephalography (EEG). The purpose of this study was to study the earliest preictal changes in children with absence epilepsy. In this report, magnetoencephalography recordings of 44 absence seizures recorded from 12 children with drug-naïve childhood absence seizures were used to perform time frequency analysis and source localization prior to the onset of the seizures. Evidence of preictal magnetoencephalography frequency changes were detected a mean of 694 ms before the initial spike on the EEG. A consistent pattern of focal sources was present in the frontal cortex and thalamus during this preictal period, but source localization occurred synchronously so that independent activity between the 2 structures could not be distinguished

Effects of chronic cannabinoid exposure during adolescence on reward preference and mPFC activation in adulthood

Cannabis is one of the most commonly used drugs among adolescents, with initial use beginning between the ages of 12 to 17. Although often perceived as a 'soft drug', both short- and long-term use have been associated with numerous adverse outcomes, including cognitive impairment, increased risk of substance abuse, and heightened risk of psychosis or schizophrenia in individuals with a predisposition. Further, the severity of these impairments is closely linked to initiation of use, i.e. earlier use increases risk. It has been suggested that adolescent vulnerability to the adverse consequences of cannabis use is due to ongoing brain development occurring during this time. Indeed, the adolescent brain continues to be remodeled well into adolescence and early adulthood, particularly in the prefrontal cortex (PFC). The medial prefrontal cortex (mPFC) has been implicated in reward processing and decision-making and alterations in mPFC development due to adolescent cannabis exposure could impair these functions. To model the effects of cannabis on mPFC function, we administered the synthetic cannabinoid WIN 55, 212-2 (WIN) to male and female rats from postnatal day 30-60. Once animals reached adulthood, we used a Probabilistic Reward (PR) choice task to elicit PFC activity and measure how patterns of activity to task-related events were modulated by adolescent WIN-treatment. Adult animals showed subtle effects of WIN-treatment on choice patterns. During task performance, mPFC activity elicited by lever press at the time of choices and reward delivery following choices were reduced in WIN-treated animals. This lasting effect of WIN suggests an impairment of the maturation of excitatory-inhibitory balance of signals in mPFC during adolescence, which may alter executive function into adulthood