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Mesolimbic Cannabinoids

Mason M Silveira, Jonathon C Arnold, Steven R Laviolette, Cecilia J Hillard, Marta Celorrio, María S Aymerich, Wendy K Adams
Public opinion surrounding the recreational use and therapeutic potential of cannabis is shifting. This review describes new work examining the behavioural and neural effects of cannabis and the endocannabinoid system, highlighting key regions within corticolimbic brain circuits. First, we consider the role of human genetic factors and cannabis strain chemotypic differences in contributing to interindividual variation in the response to cannabinoids, such as THC, and review studies demonstrating that THC-induced impairments in decision-making processes are mediated by actions at prefrontal CB1 receptors...
September 14, 2016: Neuroscience and Biobehavioral Reviews
Linda Patia Spear
Studies using animal models of adolescent exposure to alcohol, nicotine, cannabinoids, and the stimulants cocaine, 3,4-methylenedioxymethampethamine and methamphetamine have revealed a variety of persisting neural and behavioral consequences. Affected brain regions often include mesolimbic and prefrontal regions undergoing notable ontogenetic change during adolescence, although it is unclear whether this represents areas of specific vulnerability or particular scrutiny to date. Persisting alterations in forebrain systems critical for modulating reward, socioemotional processing and cognition have emerged, including apparent induction of a hyper-dopaminergic state with some drugs and/or attenuations in neurons expressing cholinergic markers...
November 2016: Neuroscience and Biobehavioral Reviews
J Ceccarini, N Weltens, H G Ly, J Tack, L Van Oudenhove, K Van Laere
Although of great public health relevance, the mechanisms underlying disordered eating behavior and body weight regulation remain insufficiently understood. Compelling preclinical evidence corroborates a critical role of the endocannabinoid system (ECS) in the central regulation of appetite and food intake. However, in vivo human evidence on ECS functioning in brain circuits involved in food intake regulation as well as its relationship with body weight is lacking, both in health and disease. Here, we measured cannabinoid 1 receptor (CB1R) availability using positron emission tomography (PET) with [(18)F]MK-9470 in 54 patients with food intake disorders (FID) covering a wide body mass index (BMI) range (anorexia nervosa, bulimia nervosa, functional dyspepsia with weight loss and obesity; BMI range=12...
2016: Translational Psychiatry
Christopher Norris, Michael Loureiro, Cecilia Kramar, Jordan Zunder, Justine Renard, Walter Rushlow, Steven R Laviolette
Emerging evidence suggests that the largest phytochemical component of cannabis, cannabidiol (CBD), may possess pharmacotherapeutic properties in the treatment of neuropsychiatric disorders. CBD has been reported to functionally interact with both the mesolimbic dopamine (DA) and serotonergic (5-HT) receptor systems. However, the underlying mechanisms by which CBD may modulate emotional processing are not currently understood. Using a combination of in vivo electrophysiological recording and fear conditioning in rats, the present study aimed to characterize the behavioral, neuroanatomical, and pharmacological effects of CBD within the mesolimbic pathway, and its possible functional interactions with 5-HT and DAergic transmission...
November 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Tasha Ahmad, Ninglei Sun, Danika Lyons, Steven R Laviolette
Functional connections between the basolateral amygdala (BLA) and nucleus accumbens (NAc) are involved critically in opiate-reward processing. In the BLA, inhibitory GABAergic substrates are inhibited by cannabinoid CB1 receptor (CB1R) activation and can modulate BLA projections to various limbic regions, including the NAc. However, the potential role of CB1R transmission in the regulation of opiate-related memory formation via the BLA → NAc circuit is not understood. Using an unbiased conditioned place preference paradigm in rats, we examined the effects of intra-BLA CB1R modulation by either direct pharmacological activation or blockade of CB1R transmission...
May 27, 2016: Addiction Biology
Benoit Forget, Mihail Guranda, Islam Gamaleddin, Steven R Goldberg, Bernard Le Foll
RATIONALE: The endocannabinoid system is composed of endocannabinoids (such as anandamide), their target receptors (CB1 and CB2 receptors, CB1Rs and CB2Rs), the enzymes that degrade them (fatty-acid-amide-hydrolase (FAAH) for anandamide), and an endocannabinoid transporter. FAAH inhibition has been recently identified as having a critical involvement in behaviors related to nicotine addiction and has been shown to reduce the effect of nicotine on the mesolimbic dopaminergic system via CB1R and peroxisome proliferator-activated receptor alpha (PPARα)...
2016: Psychopharmacology
Andrea Ossato, Isabella Canazza, Claudio Trapella, Fabrizio Vincenzi, Maria Antonietta De Luca, Claudia Rimondo, Katia Varani, Pier Andrea Borea, Giovanni Serpelloni, Matteo Marti
JWH-250 and JWH-073 are two synthetic cannabinoid agonists with nanomolar affinity at CB1 and CB2 receptors. They are illegally marketed within "herbal blend" for theirs psychoactive effects greater than those produced by Cannabis. Recently, we analyzed an "herbal" preparation containing a mixture of both JWH-250 and JWH-073. The present study was aimed at investigating the in vitro and in vivo pharmacological activity of JWH-250 and JWH-073 in male CD-1 mice. In vitro competition binding experiments performed on mouse and human CB1 and CB2 receptors revealed a nanomolar affinity and potency of the JWH-250 and JWH-073...
June 3, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
Michael Loureiro, Cecilia Kramar, Justine Renard, Laura G Rosen, Steven R Laviolette
BACKGROUND: Cannabinoid receptor transmission strongly influences emotional processing, and disturbances in cannabinoid signaling are associated with various neuropsychiatric disorders. The mammalian ventral hippocampus (vHipp) is a critical neural region controlling mesolimbic activity via glutamatergic projections to the nucleus accumbens. Furthermore, vHipp abnormalities are linked to schizophrenia-related psychopathology. Nevertheless, the mechanisms by which intra-vHipp cannabinoid signaling may modulate mesolimbic activity states and emotional processing are not currently understood...
August 1, 2016: Biological Psychiatry
Maria Scherma, Christian Dessì, Anna Lisa Muntoni, Salvatore Lecca, Valentina Satta, Antonio Luchicchi, Marco Pistis, Leigh V Panlilio, Liana Fattore, Steven R Goldberg, Walter Fratta, Paola Fadda
Cannabis is the most commonly used illicit drug worldwide, and use is typically initiated during adolescence. The endocannabinoid system has an important role in formation of the nervous system, from very early development through adolescence. Cannabis exposure during this vulnerable period might lead to neurobiological changes that affect adult brain functions and increase the risk of cannabis use disorder. The aim of this study was to investigate whether exposure to Δ(9)-tetrahydrocannabinol (THC) in adolescent rats might enhance reinforcing effects of cannabinoids in adulthood...
April 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Sabine C Herpertz, Katja Bertsch
Borderline personality disorder is characterized by three domains of dysfunction: affect dysregulation, behavioral dyscontrol, and interpersonal hypersensitivity. Interpersonal hypersensitivity is associated with a (pre)attentive bias toward negative social information and, on the level of the brain, enhanced bottom-up emotion generation, while affect dysregulation results from abnormal top-down processes. Additionally, the problems of patients with borderline personality disorder in interpersonal functioning appear to be related to alterations in the (social) reward and empathy networks...
September 1, 2015: American Journal of Psychiatry
Mohammad-Reza Zarrindast, Fatemeh Khakpai
Anxiety is an unpleasant physiological state in which an overreaction to a situation occurs. It has been suggested that different brain regions are involved in the modulation and expression of anxiety, including the amygdala, hippocampus, and frontal cortex. Dysfunction of neurotransmitters and their receptors can lead to many mood disorders like anxiety. There are evidences that dopamine plays an important role in anxiety modulation in different parts of the brain. Some evidence has shown that the mesolimbic, mesocortical and nigrostriatal dopaminergic system are involved in anxiety...
September 2015: Archives of Iranian Medicine
Anna Zdanowicz, Wieńczysław Kaźmierczak, Piotr Wierzbiński
Excessive consumption and obesity do not always have to be strictly pathological. The adjustment of food intake as well as the pleasure of eating are the results of the circulation of neurotransmitters, hormones and glucocorticoids which have an ability to regulate the activity of many receptors connected with G protein, including endocannabinoid receptors. The key role of endocannabinoids in pathogenesis of obesity is their overproduction by adipose cells. Endocannabinoids (eCBs) affect CB1 receptors and increase hunger, willingness to intake food, decrease peristalsis and delay stomach emptying...
July 2015: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
Ricardo Jorge Dinis-Oliveira
Drugs of abuse are a heterogeneous group of xenobiotics or endobiotics that alter synaptic organization in the central nervous system in a transient or permanent basis, often leading to a compulsively use. What unites its members is that they confer pleasure (hedonism) to the abusers, namely by their action in the mesolimbic dopamine system. To exert its effects, different drugs of abuse will act on receptors and neurotransmitter transporters, modeling neurotransmitter release into the synaptic cleft. Besides acting on presynaptic neurons also function in neurotransmitter receptors and ion channels in postsynaptic neurons, thereby modifying the signaling pathways...
November 2014: Acta Médica Portuguesa
Michael Loureiro, Justine Renard, Jordan Zunder, Steven R Laviolette
Disturbances in cannabinoid type 1 receptor (CB1R) signaling have been linked to emotional and cognitive deficits characterizing neuropsychiatric disorders, including schizophrenia. Thus, there is growing interest in characterizing the relationship between cannabinoid transmission, emotional processing, and dopamine (DA)-dependent behavioral deficits. The CB1R is highly expressed in the mammalian nervous system, particularly in the hippocampus. Activation of the ventral hippocampal subregion (vHipp) is known to increase both the activity of DAergic neurons located in the ventral tegmental area (VTA) and DA levels in reward-related brain regions, particularly the nucleus accumbens (NAc)...
May 2015: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Ginetta Collo, Laura Cavalleri, PierFranco Spano
Mesencephalic dopaminergic neurons were suggested to be a critical physiopathology substrate for addiction disorders. Among neuroadaptive processes to addictive drugs, structural plasticity has attracted attention. While structural plasticity occurs at both pre- and post-synaptic levels in the mesolimbic dopaminergic system, the present review focuses only on dopaminergic neurons. Exposures to addictive drugs determine two opposite structural responses, hypothrophic plasticity produced by opioids and cannabinoids (in particular during the early withdrawal phase) and hypertrophic plasticity, mostly driven by psychostimulants and nicotine...
2014: Frontiers in Pharmacology
Dan P Covey, Jennifer M Wenzel, Joseph F Cheer
Marijuana is the most popular illegal drug worldwide. Recent trends indicate that this may soon change; not due to decreased marijuana use, but to an amendment in marijuana's illegal status. The cannabinoid type 1 (CB1) receptor mediates marijuana's psychoactive and reinforcing properties. CB1 receptors are also part of the brain endocannabinoid (eCB) system and support numerous forms of learning and memory, including the conditioned reinforcing properties of cues predicting reward or punishment. This is accomplished via eCB-dependent alterations in mesolimbic dopamine function, which plays an obligatory role in reward learning and motivation...
December 2, 2015: Brain Research
Jason M Wiebelhaus, Travis W Grim, Robert A Owens, Matthew F Lazenka, Laura J Sim-Selley, Rehab A Abdullah, Micah J Niphakis, Robert E Vann, Benjamin F Cravatt, Jenny L Wiley, S Stevens Negus, Aron H Lichtman
A growing body of evidence implicates endogenous cannabinoids as modulators of the mesolimbic dopamine system and motivated behavior. Paradoxically, the reinforcing effects of Δ(9)-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, have been difficult to detect in preclinical rodent models. In this study, we investigated the impact of THC and inhibitors of the endocannabinoid hydrolytic enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) on operant responding for electrical stimulation of the medial forebrain bundle [intracranial self-stimulation (ICSS)], which is known to activate the mesolimbic dopamine system...
February 2015: Journal of Pharmacology and Experimental Therapeutics
Brittany Draycott, Michael Loureiro, Tasha Ahmad, Huibing Tan, Jordan Zunder, Steven R Laviolette
Disturbances in cortical cannabinoid CB1 receptor signaling are well established correlates of various neuropsychiatric disorders, including depression and schizophrenia. Importantly, the ability of cannabinoid transmission to modulate emotional processing is functionally linked to interactions with subcortical DA systems. While considerable evidence demonstrates that CB1 receptor-mediated modulation of emotional processing and related behaviors follows a biphasic functional curve, little is known regarding how CB1 signaling within cortical networks may interact with subcortical DAergic systems involved in emotional behavior regulation...
September 24, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jennifer M Wenzel, Joseph F Cheer
The mesolimbic dopamine (DA) system plays an integral role in incentive motivation and reward seeking and a growing body of evidence identifies signal transduction at cannabinoid receptors as a critical modulator of this system. Indeed, administration of exogenous cannabinoids results in burst firing of DA neurons of the ventral tegmental area and increases extracellular DA in the nucleus accumbens (NAcc). Implementation of fast-scan cyclic voltammetry (FSCV) confirms the ability of cannabinoids to augment DA within the NAcc on a subsecond timescale...
2014: Frontiers in Psychiatry
Huibing Tan, Tasha Ahmad, Michael Loureiro, Jordan Zunder, Steven R Laviolette
Emerging evidence from both basic and clinical research demonstrates an important role for endocannabinoid (ECB) signaling in the processing of emotionally salient information, learning, and memory. Cannabinoid transmission within neural circuits involved in emotional processing has been shown to modulate the acquisition, recall, and extinction of emotionally salient memories and importantly, can strongly modulate the emotional salience of incoming sensory information. Two neural regions in particular, the medial prefrontal cortex (PFC) and the basolateral nucleus of the amygdala (BLA), play important roles in emotional regulation and contain high levels of cannabinoid receptors...
2014: Frontiers in Psychiatry
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