Endocannabinoid system contributions to sex-specific adolescent neurodevelopment.

With an increasing number of countries and states adopting legislation permitting the use of cannabis for medical purposes, there is a growing interest among health and research professionals into the system through which cannabinoids principally act, the endocannabinoid system (ECS). Much of the seminal research into the ECS dates back only 30 years and, although there has been tremendous development within the field during this time, many questions remain. More recently, investigations have emerged examining the contributions of the ECS to normative development and the effect of altering this system during important critical periods.

The Endocannabinoid System and Invertebrate Neurodevelopment and Regeneration.

Cannabis has long been used for its medicinal and psychoactive properties. With the relatively new adoption of formal medicinal cannabis regulations worldwide, the study of cannabinoids, both endogenous and exogenous, has similarly flourished in more recent decades. In particular, research investigating the role of cannabinoids in regeneration and neurodevelopment has yielded promising results in vertebrate models.

Dissociable changes in spike and wave discharges following exposure to injected cannabinoids and smoked cannabis in Genetic Absence Epilepsy Rats from Strasbourg.

There is significant interest in the use of cannabinoids for the treatment of many epilepsies including absence epilepsy (AE). Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model many aspects of AE including the presence of spike-and-wave discharges (SWDs) on electroencephalogram (EEG) and behavioral comorbidities, such as elevated anxiety. However, the effects of cannabis plant-based phytocannabinoids have not been tested in GAERS.

Adolescent CB1 receptor antagonism influences subsequent social interactions and neural activity in female rats.

We previously demonstrated that repeated exposure to the CB1 receptor antagonist/inverse agonist AM251 in adolescence (PND 30-44) increased social interactions in female rats when tested 48 h after the final exposure to the antagonist. Here, we investigated whether the increased sociality would be present after a longer drug washout period (5 days) in both male and female rats (experiment 1), and sought to identify candidate brain regions that may explain the observed differences in social behaviours between AM251 and vehicle-treated female rats (experiment 2). While drug-free, adolescent AM251 treatment increased social interactions in females and not in males.

Cannabinoids in Chronic Non-Cancer Pain: A Systematic Review and Meta-Analysis.

Background: For patients with chronic, non-cancer pain, traditional pain-relieving medications include opioids, which have shown benefits but are associated with increased risks of addiction and adverse effects. Medical cannabis has emerged as a treatment alternative for managing these patients and there has been a rise in the number of randomized clinical trials in recent years; therefore, a systematic review of the evidence was warranted.

Objective: To analyze the evidence surrounding the benefits and harms of medical cannabinoids in the treatment of chronic, non-cancer-related pain.

Effects of long-term dietary administration of estrogen receptor-beta agonist diarylpropionitrile on ovariectomized female ICR (CD-1) mice.

Diarylpropionitrile (DPN) is an estrogen receptor-β-specific agonist that has been linked to neuroprotection, preserving cognitive function with age, the suppression of anxiety-like behaviors, inhibition of cancer growth, and other positive properties. We hypothesized that DPN may have pro-longevity properties. DPN was administered via feed at a dose corresponding to approximately 3 mg/kg/day to ovariectomized female mice beginning at 7 months of age.

Sex-specific effects of CB1 receptor antagonism and stress in adolescence on anxiety, corticosterone concentrations, and contextual fear in adulthood in rats.

There is a paucity of research regarding the role of endogenous cannabinoid signalling in adolescence on brain and behaviour development. We previously demonstrated effects of repeated CB1 receptor antagonism in adolescence on socioemotional behaviours and neural protein expression 24-48 h after the last drug administration in female rats, with no effect in males. Here we investigate whether greater effects would be manifested after a lengthier delay.

Effects of CB1 receptor antagonism and stress exposures in adolescence on socioemotional behaviours, neuroendocrine stress responses, and expression of relevant proteins in the hippocampus and prefrontal cortex in rats.

Little is known about the consequences of altered endocannabinoid signalling in adolescence. We hypothesized that CB1 receptor antagonism (AM251, 1 mg/kg) and stress exposures (1 h confinement stress) in adolescence (daily, postnatal days 30-44) would interact to increase neuroendocrine stress responses and anxiety when investigated a minimum of 24 h after drug and stress treatments; these treatment effects were independent of each other. Changes in homecage behaviour and in weight gain confirmed that both males and females were sensitive to the treatments.

Translational relevance of rodent models of hypothalamic-pituitary-adrenal function and stressors in adolescence.

Elevations in glucocorticoids that result from environmental stressors can have programming effects on brain structure and function when the exposure occurs during sensitive periods that involve heightened neural development. In recent years, adolescence has gained increasing attention as another sensitive period of development, a period in which pubertal transitions may increase the vulnerability to stressors. There are similarities in physical and behavioural development between humans and rats, and rats have been used effectively as an animal model of adolescence and the unique plasticity of this period of ontogeny.

Intracellular signalling and plasma hormone profiles associated with the expression of unconditioned and conditioned fear and anxiety in female rats.

There is considerable overlap in the neural regions and intracellular signalling pathways implicated in anxiety and fear, although less is known in females. Here, we investigated whether unconditioned and conditioned fear are associated with distinct patterns of expression of extracellular signal-regulated kinase-1 and -2 (ERK1/2), protein kinase B (Akt), and calcineurin (CaN) (proteins that are key regulators of the expression of and/or memory processes of fear and anxiety) in the dorsal and ventral hippocampus, medial prefrontal cortex, and amygdala (important regions in neural fear circuitry) of adult female rats, and used a multivariate approach to find patterns of signalling that might discriminate between the different states of fear. To isolate fear to the conditioned cue from generalized fear to the test context, rats were conditioned to an auditory tone (i.

Glucocorticoid receptor translocation and expression of relevant genes in the hippocampus of adolescent and adult male rats.

We investigated whether pre-pubertal (postnatal day [P] 35) and post-pubertal adolescent (P45) and adult (P75) male rats differed in stressor-induced hormonal responses and in glucocorticoid receptor (GR) translocation because it has been proposed that negative feedback is maturing in adolescence and may be a basis for the prolonged activation of the HPA axis in adolescents compared with adults. The three age groups did not differ at baseline in plasma corticosterone or progesterone concentrations, and P35 had lower concentrations of testosterone than did both P45 and P75 rats, which did not differ. After 30min of restraint stress, plasma concentrations of corticosterone and progesterone increased to a greater extent in the adolescents than in the adults.

Differential effects of CB1 receptor agonism in behavioural tests of unconditioned and conditioned fear in adult male rats.

We investigated the effects of the highly selective CB1 receptor agonist ACEA and the CB1 receptor antagonist/inverse agonist AM251 on two behavioural tests of unconditioned fear, the elevated plus maze (EPM) and open field test (OFT), as well as on the recall and extinction of a conditioned auditory fear. Both ACEA and AM251 increased anxiety-like behaviour in the EPM and OFT. There was no effect of either drug on recall of the conditioned fear, and ACEA enhanced and AM251 impaired fear extinction.

Peer pressures: social instability stress in adolescence and social deficits in adulthood in a rodent model.

Studies in animal models generate and test hypotheses regarding developmental stage-specific vulnerability that might inform research questions about human development. In both rats and humans, peer relationships are qualitatively different in adolescence than at other stages of development, and social experiences in adolescence are considered important determinants of adult social function. This review describes our adolescent rat social instability stress model and the long-lasting effects social instability has on social behaviour in adulthood as well as the possible neural underpinnings.

Effects of social context on endocrine function and Zif268 expression in response to an acute stressor in adolescent and adult rats.

There is a paucity of studies comparing social buffering in adolescents and adults, despite their marked differences in social behavior. We investigated whether greater effects of social buffering on plasma corticosterone concentrations and expression of Zif268 in neural regions after an acute stressor would be found in adolescent than adult rats. Samples were obtained before and after 1h of isolation stress and after either 1 or 3h of recovery back in the colony with either a familiar or unfamiliar cage partner.