scholarly journals Discordant Effects of Cannabinoid 2 Receptor Antagonism/Inverse Agonism During Adolescence on Pavlovian and Instrumental Reward Learning in Adult Male Rats

2021 ◽  
Vol 13 ◽  
Author(s):  
Danna Ellner ◽  
Bryana Hallam ◽  
Jude A. Frie ◽  
Hayley H. A. Thorpe ◽  
Muhammad Shoaib ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Critical Role ◽  
Behavioral Outcomes ◽  
Endocannabinoid System ◽  
Developmental Trajectory ◽  
Male Rats ◽  
Reward Learning ◽  
Adolescent Male ◽  
High Dose ◽  
Lever Pressing

The endocannabinoid system is responsible for regulating a spectrum of physiological activities and plays a critical role in the developing brain. During adolescence, the endocannabinoid system is particularly sensitive to external insults that may change the brain’s developmental trajectory. Cannabinoid receptor type 2 (CB2R) was initially thought to predominantly function in the peripheral nervous system, but more recent studies have implicated its role in the mesolimbic pathway, a network largely attributed to reward circuitry and reward motivated behavior, which undergoes extensive changes during adolescence. It is therefore important to understand how CB2R modulation during adolescence can impact reward-related behaviors in adulthood. In this study, adolescent male rats (postnatal days 28–41) were exposed to a low or high dose of the CB2R antagonist/inverse agonist SR144528 and Pavlovian autoshaping and instrumental conditional behavioral outcomes were measured in adulthood. SR144528-treated rats had significantly slower acquisition of the autoshaping task, seen by less lever pressing behavior over time [F(2, 19) = 5.964, p = 0.010]. Conversely, there was no effect of adolescent SR144528 exposure on instrumental conditioning. These results suggest that modulation of the CB2R in adolescence differentially impacts reward-learning behaviors in adulthood.

scholarly journals THC Exposure is Reflected in the Microstructure of the Cerebral Cortex and Amygdala of Young Adults

2020 ◽  
Vol 30 (9) ◽  
pp. 4949-4963 ◽  
Author(s):  
Ryan P Cabeen ◽  
John M Allman ◽  
Arthur W Toga
Keyword(s):  
Young Adults ◽  
Cerebral Cortex ◽  
Molecular Mechanisms ◽  
Cannabinoid Receptor ◽  
Memory Performance ◽  
Critical Role ◽  
Endocannabinoid System ◽  
Imaging Data ◽  
Brain Areas ◽  
Human Connectome Project

Abstract The endocannabinoid system serves a critical role in homeostatic regulation through its influence on processes underlying appetite, pain, reward, and stress, and cannabis has long been used for the related modulatory effects it provides through tetrahydrocannabinol (THC). We investigated how THC exposure relates to tissue microstructure of the cerebral cortex and subcortical nuclei using computational modeling of diffusion magnetic resonance imaging data in a large cohort of young adults from the Human Connectome Project. We report strong associations between biospecimen-defined THC exposure and microstructure parameters in discrete gray matter brain areas, including frontoinsular cortex, ventromedial prefrontal cortex, and the lateral amygdala subfields, with independent effects in behavioral measures of memory performance, negative intrusive thinking, and paternal substance abuse. These results shed new light on the relationship between THC exposure and microstructure variation in brain areas related to salience processing, emotion regulation, and decision making. The absence of effects in some other cannabinoid-receptor-rich brain areas prompts the consideration of cellular and molecular mechanisms that we discuss. Further studies are needed to characterize the nature of these effects across the lifespan and to investigate the mechanistic neurobiological factors connecting THC exposure and microstructural parameters.

scholarly journals High-Dose Testosterone Propionate Treatment Reverses the Effects of Endurance Training on Myocardial Antioxidant Defenses in Adolescent Male Rats

2011 ◽  
Vol 11 (2) ◽  
pp. 118-127 ◽  
Author(s):  
Ewa Sadowska-Krępa ◽  
Barbara Kłapcińska ◽  
Sławomir Jagsz ◽  
Andrzej Sobczak ◽  
Stanisław J. Chrapusta ◽  
...  
Keyword(s):  
Endurance Training ◽  
Testosterone Propionate ◽  
Male Rats ◽  
Antioxidant Defenses ◽  
Adolescent Male ◽  
High Dose

scholarly journals Acute effects of endocannabinoid anandamide and CB1 receptor antagonist, AM251 in the regulation of thyrotropin secretion

2008 ◽  
Vol 199 (2) ◽  
pp. 235-242 ◽  
Author(s):  
Marco Aurélio Liberato Costa da Veiga ◽  
Flávia Fonseca Bloise ◽  
Ricardo Henrique Costa-e-Sousa ◽  
Luana Lopes Souza ◽  
Norma Aparecida dos Santos Almeida ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Receptor Antagonist ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Fold Increase ◽  
Inhibitory Effect ◽  
Negative Regulator ◽  
Male Rats ◽  
Acute Effects ◽  
Serum Tsh

We examined the acute effects of endocannabinoid, anandamide, and of synthetic cannabinoid receptor antagonist, AM251[N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide], on TSH, thyroxine (T4), and triiodothyronine (T3) secretions. Euthyroid male rats showed a 42% decrease in serum TSH, 2 h after a single i.p. injection of 0.02, but not 0.2 mg/kg body weight (BW), anandamide, accompanied by a 39% reduction in serum T4, without alteration in serum T3. At 0.5 and 1 h, these serum hormones showed no significant change. Hypothyroid rats showed a 35% reduction in serum TSH (P<0.01), 2 h after anandamide injection, which had no effect on hyperthyroid rats. In both thyroid states, no modification of serum thyroid hormones was observed. Intraperitoneal injection of 0.17 or 1.7 mg/kg BW AM251 in euthyroid rats caused, 1.5 h later, 1.7-fold or 4.3-fold increase in serum TSH respectively, without changing thyroid hormones. Stimulatory effect of 0.17 mg/kg BW AM251 and inhibitory effect of anandamide was abolished in the group injected with AM251 followed by an anandamide injection, 30 min later. Intracerebroventricular injection of 20 ng (but not 200 ng) anandamide induced a decrease in serum TSH at 60 min after injection, which tended to disappear at 120 min. Anterior pituitary explants presented significant reduction in TSH release in the presence of 10−7 M anandamide in incubation medium, which was blocked by 10−7 M AM251. In conclusion, anandamide has the ability to acutely inhibit TSH release in eu- and hypothyroid rats, acting at the hypothalamus–pituitary axis. Since, in addition, the cannabinoid receptor antagonist AM251 increased TSH release, we suggest that endocannabinoid system has a role as negative regulator of TSH secretion.

scholarly journals CB1 antagonism increases excitatory synaptogenesis in a cortical spheroid model of fetal brain development

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexis Papariello ◽  
David Taylor ◽  
Ken Soderstrom ◽  
Karen Litwa
Keyword(s):  
Brain Development ◽  
Spontaneous Activity ◽  
Microelectrode Array ◽  
Cannabinoid Receptor ◽  
Fetal Brain ◽  
Endocannabinoid System ◽  
Autism Spectrum ◽  
Nervous System Development ◽  
Inhibitory Synapses ◽  
Fetal Brain Development

AbstractThe endocannabinoid system (ECS) plays a complex role in the development of neural circuitry during fetal brain development. The cannabinoid receptor type 1 (CB1) controls synaptic strength at both excitatory and inhibitory synapses and thus contributes to the balance of excitatory and inhibitory signaling. Imbalances in the ratio of excitatory to inhibitory synapses have been implicated in various neuropsychiatric disorders associated with dysregulated central nervous system development including autism spectrum disorder, epilepsy, and schizophrenia. The role of CB1 in human brain development has been difficult to study but advances in induced pluripotent stem cell technology have allowed us to model the fetal brain environment. Cortical spheroids resemble the cortex of the dorsal telencephalon during mid-fetal gestation and possess functional synapses, spontaneous activity, an astrocyte population, and pseudo-laminar organization. We first characterized the ECS using STORM microscopy and observed synaptic localization of components similar to that which is observed in the fetal brain. Next, using the CB1-selective antagonist SR141716A, we observed an increase in excitatory, and to a lesser extent, inhibitory synaptogenesis as measured by confocal image analysis. Further, CB1 antagonism increased the variability of spontaneous activity within developing neural networks, as measured by microelectrode array. Overall, we have established that cortical spheroids express ECS components and are thus a useful model for exploring endocannabinoid mediation of childhood neuropsychiatric disease.

scholarly journals Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3389
Author(s):  
Ishtiaq Ahmed ◽  
Saif Ur Rehman ◽  
Shiva Shahmohamadnejad ◽  
Muhammad Anjum Zia ◽  
Muhammad Ahmad ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Cell Types ◽  
Autoimmune Disorders ◽  
Specific Receptors ◽  
Different Cell Types

In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer—both in vivo and in vitro clinical trials—has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

scholarly journals Early Consumption of Cannabinoids: From Adult Neurogenesis to Behavior

2021 ◽  
Vol 22 (14) ◽  
pp. 7450
Author(s):  
Citlalli Netzahualcoyotzi ◽  
Luis Miguel Rodríguez-Serrano ◽  
María Elena Chávez-Hernández ◽  
Mario Humberto Buenrostro-Jáuregui
Keyword(s):  
Young Adulthood ◽  
Adult Neurogenesis ◽  
Critical Period ◽  
Consumption Rate ◽  
Behavioral Outcomes ◽  
Endocannabinoid System ◽  
Illegal Drug ◽  
Adult Brain ◽  
As Stress

The endocannabinoid system (ECS) is a crucial modulatory system in which interest has been increasing, particularly regarding the regulation of behavior and neuroplasticity. The adolescent–young adulthood phase of development comprises a critical period in the maturation of the nervous system and the ECS. Neurogenesis occurs in discrete regions of the adult brain, and this process is linked to the modulation of some behaviors. Since marijuana (cannabis) is the most consumed illegal drug globally and the highest consumption rate is observed during adolescence, it is of particular importance to understand the effects of ECS modulation in these early stages of adulthood. Thus, in this article, we sought to summarize recent evidence demonstrating the role of the ECS and exogenous cannabinoid consumption in the adolescent–young adulthood period; elucidate the effects of exogenous cannabinoid consumption on adult neurogenesis; and describe some essential and adaptive behaviors, such as stress, anxiety, learning, and memory. The data summarized in this work highlight the relevance of maintaining balance in the endocannabinoid modulatory system in the early and adult stages of life. Any ECS disturbance may induce significant modifications in the genesis of new neurons and may consequently modify behavioral outcomes.

scholarly journals Adolescent male rats exposed to social defeat exhibit altered anxiety behavior and limbic monoamines as adults.

2009 ◽  
Vol 123 (3) ◽  
pp. 564-576 ◽  
Author(s):  
Michael J. Watt ◽  
Andrew R. Burke ◽  
Kenneth J. Renner ◽  
Gina L. Forster
Keyword(s):  
Social Defeat ◽  
Male Rats ◽  
Adolescent Male ◽  
Anxiety Behavior

scholarly journals Effects of Hexachlorocyclohexane (HCH-γ-Isomer, Lindane) Intoxication on the Proliferation and Apoptosis in Rat Testes

2009 ◽  
Vol 78 (4) ◽  
pp. 615-620 ◽  
Author(s):  
Hayati Yuksel ◽  
Erkan Karadas ◽  
Hikmet Keles ◽  
Hasan Huseyin Demirel
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Male Rats ◽  
Control Group ◽  
High Dose ◽  
Histopathological Changes ◽  
Proliferation And Apoptosis ◽  
Group A ◽  
Higher Doses ◽  
Group 1

In this study, experimentally lindane-induced histopathological changes and proliferation and/or apoptosis in germ cells in the rat testes were investigated. A total of 40 healthy fertile 3-month-old male rats were used. Animals were divided into 4 groups, each containing 10 rats. Group 1 (control) was given only pure olive oil, Groups 2, 3 and 4 were administered lindane at 10, 20 and 40 mg/kg/bw, respectively, by gastric gavage for 30 days. Microscopically, degenerative changes were observed in the lindane-treated groups. For proliferative activity PCNA immunolabelling and for germ cells apoptosis TUNEL methods were performed. Although a strong PCNA positivity in the control group was observed, a gradual decrease was noted in the lindane-treated groups especially at higher doses. Significant increases of apoptosis were seen in the lindane-treated groups compared to the control group. A decrease in testosterone concentrations was observed in lindane-treated groups compared to the control group. The study indicates that high-dose lindane intoxication contributes to the suppression of spermatogenesis through a reduction of germ cell proliferation and an increase of germ cell death in rat testes.

Effect of gallic acid on the reproduction of adolescent male Brandt’s vole (Lasiopodomys brandtii)

2021 ◽  
Author(s):  
Xin Dai ◽  
Xiao-Feng Sun ◽  
Ai-Qin Wang ◽  
Wanhong Wei ◽  
Sheng-Mei Yang
Keyword(s):  
Gallic Acid ◽  
Low Dose ◽  
Regulatory Protein ◽  
Antioxidant Properties ◽  
Adolescent Male ◽  
Seminiferous Tubules ◽  
High Dose ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Lasiopodomys Brandtii

Gallic acid (GA), a phenol that is present in various plants, potentially contains antioxidant properties. This study aimed to investigate the effects of GA on the reproduction of adolescent male Brandt’s voles (Lasiopodomys brandtii (Radde, 1861)). Antioxidant levels and apoptosis in the testis, as well as reproductive physiology, were evaluated in adolescent males treated with GA. The results showed that a low dose of GA enhanced relative epididymis weight and the sperm density in the epididymis, increased the mRNA levels of steroidogenic acute regulatory protein in the testis, and reduced the percentages of abnormal and dead sperm. In addition, a low dose of GA significantly increased the levels of superoxide dismutase, catalase, and glutathione peroxidase, and decreased the level of malondialdehyde in the testis, as well as the mRNA and protein levels of the apoptosis related gene, caspase-3. However, a high dose of GA sharply reduced the average diameter of the seminiferous tubules compared to a low dose. Collectively, these findings demonstrate that GA treatment during puberty affects the reproductive responses of male Brandt’s voles in a dose-dependent manner by regulating antioxidant levels and apoptosis.

Excitation of Putative Glutamatergic Neurons in the Rat Parabrachial Nucleus Region Reduces Delta Power during Dexmedetomidine but not Ketamine Anesthesia

2021 ◽  
Author(s):  
Eric D. Melonakos ◽  
Morgan J. Siegmann ◽  
Charles Rey ◽  
Christopher O’Brien ◽  
Ksenia K. Nikolaeva ◽  
...  
Keyword(s):  
Recovery Time ◽  
Low Dose ◽  
Designer Drugs ◽  
Male Rats ◽  
Parabrachial Nucleus ◽  
High Dose ◽  
Median Difference ◽  
Delta Power ◽  
Calcium Calmodulin Dependent ◽  
Ketamine Anesthesia

Background Parabrachial nucleus excitation reduces cortical delta oscillation (0.5 to 4 Hz) power and recovery time associated with anesthetics that enhance γ-aminobutyric acid type A receptor action. The effects of parabrachial nucleus excitation on anesthetics with other molecular targets, such as dexmedetomidine and ketamine, remain unknown. The hypothesis was that parabrachial nucleus excitation would cause arousal during dexmedetomidine and ketamine anesthesia. Methods Designer Receptors Exclusively Activated by Designer Drugs were used to excite calcium/calmodulin–dependent protein kinase 2α–positive neurons in the parabrachial nucleus region of adult male rats without anesthesia (nine rats), with dexmedetomidine (low dose: 0.3 µg · kg−1 · min−1 for 45 min, eight rats; high dose: 4.5 µg · kg−1 · min−1 for 10 min, seven rats), or with ketamine (low dose: 2 mg · kg−1 · min−1 for 30 min, seven rats; high dose: 4 mg · kg−1 · min−1 for 15 min, eight rats). For control experiments (same rats and treatments), the Designer Receptors Exclusively Activated by Designer Drugs were not excited. The electroencephalogram and anesthesia recovery times were recorded and analyzed. Results Parabrachial nucleus excitation reduced delta power in the prefrontal electroencephalogram with low-dose dexmedetomidine for the 150-min analyzed period, excepting two brief periods (peak median bootstrapped difference [clozapine-N-oxide – saline] during dexmedetomidine infusion = −6.06 [99% CI = −12.36 to −1.48] dB, P = 0.007). However, parabrachial nucleus excitation was less effective at reducing delta power with high-dose dexmedetomidine and low- and high-dose ketamine (peak median bootstrapped differences during high-dose [dexmedetomidine, ketamine] infusions = [−1.93, −0.87] dB, 99% CI = [−4.16 to −0.56, −1.62 to −0.18] dB, P = [0.006, 0.019]; low-dose ketamine had no statistically significant decreases during the infusion). Recovery time differences with parabrachial nucleus excitation were not statistically significant for dexmedetomidine (median difference for [low, high] dose = [1.63, 11.01] min, 95% CI = [−20.06 to 14.14, −20.84 to 23.67] min, P = [0.945, 0.297]) nor low-dose ketamine (median difference = 12.82 [95% CI: −3.20 to 39.58] min, P = 0.109) but were significantly longer for high-dose ketamine (median difference = 11.38 [95% CI: 1.81 to 24.67] min, P = 0.016). Conclusions These results suggest that the effectiveness of parabrachial nucleus excitation to change the neurophysiologic and behavioral effects of anesthesia depends on the anesthetic’s molecular target. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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