Increased motivation for beer in rats following administration of a cannabinoid CB1 receptor agonist

Gallate, Jason; Saharov, Tanya; Mallet, Paul E.; McGregor, Iain S.

doi:10.1016/s0014-2999(99)00170-3

Cited by 219 publications

(125 citation statements)

References 30 publications

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“…This is in line with the very well characterised stimulatory effects on food intake following CB1 receptor activation (Williams et al 1998;Gomez et al 2002). Previous reports showed that administration of direct cannabinoid receptor agonists like CP 55,940 and WIN 55,212-2 increases alcohol intake and alcohol reinforcement in both nonselected and genetically selected alcoholpreferring rats (Colombo et al 2002;Gallate et al 1999). These effects are mediated by activation of CB1 receptors because they are abolished by pre-treatment with the selective CB1 receptor antagonist rimonabant.…”

Section: Discussionsupporting

confidence: 84%

“…We speculate that drugs like URB597 or other endocannabinoid modulators may offer important advantages over drugs that activate CB1 receptors directly. For instance, CB1 receptor direct agonists show intrinsic abuse potential and increase consumption of other drugs of abuse (Colombo et al 2002;Gallate et al 1999;McGregor et al 2005). Conversely, as shown here, modulation of endogenous anandamide levels did not increase alcohol abuse-related behaviours.…”

Section: Discussionsupporting

confidence: 51%

“…One of the major concerns with the use of CB1 receptor agonists comes from results showing that these compounds may have abuse potential and increase intake of other drugs of abuse, especially alcohol. It is known, for example, that in rodents, direct activation of CB1 receptors by CP 55,940 and WIN 55,212-2 dose dependently increase voluntary alcohol consumption (Colombo et al 2002(Colombo et al , 2004 and alcohol drinking motivation (Gallate et al 1999), while Δ 9 -THC significantly reinstates responding previously reinforced with beer (McGregor et al 2005). Administration of the CB1 receptor agonist WIN 55,212-2 during abstinence was also shown to increase alcohol consumption when the alcoholic solution was made available again (López-Moreno et al 2004).…”

Section: Introductionmentioning

confidence: 99%

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Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat

et al. 2008

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Rationale A major clinical concern with the use of cannabinoid receptor 1 (CB1) direct agonists is that these compounds increase alcohol drinking and drug abuserelated behaviours. As an alternative approach, CB1-receptor-mediated activity can be facilitated by increasing anandamide levels with the use of hydrolase fatty acid amide hydrolase (FAAH) inhibitors. Objective Using the selective FAAH inhibitor URB597, we investigated whether activation of the endogenous cannabinoid tone increases alcohol abuse liability, as what happens with the CB1 receptor direct agonists.Materials and methods URB597 was tested on alcohol self-administration in Wistar rats and on homecage alcohol drinking in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats. In Wistar rats, URB597 effects on alcohol-induced anxiety and on stress-, yohimbineand cue-induced reinstatement of alcohol seeking were also evaluated. For comparison, the effect of the CB1 receptor antagonist rimonabant on ethanol self-administration was also tested. Results Under our experimental condition, intraperitoneal (IP) administration of URB597 (0.0, 0.3 and 1.0 mg/kg) neither increased voluntary homecage alcohol drinking in msP rats nor facilitated fixed ratio 1 and progressive ratio alcohol self-administration in nonselected Wistars. In the reinstatement tests, the compound did not have effects on cue-, footshock stress-and yohimbine-induced relapse. Conversely, URB597 completely abolished the anxiogenic response measured during withdrawal after an acute IP administration of alcohol (3.0 g/kg). Rimonabant (0.0, 0.3, 1.0 and 3.0 mg/kg) significantly reduced ethanol self-administration. Conclusions Results demonstrate that activation of the endocannabinoid anandamide system by selective inhibition of FAAH does not increase alcohol abuse risks but does reduce anxiety associated to alcohol withdrawal. We thus can speculate that medication based on the use of endocannabinoid system modulators such as URB597 may offer important advantages compared to treatment with direct CB1 receptor activators.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

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Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat

et al. 2008

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“…37 The actions of CB1 activation to increase DA signaling are consistent with the behavioral effects of CB1 agonism to increase breakpoints in a progressive ratio task for sucrose solution; therefore, rats are willing to work harder to get access to rewarding sucrose after CB1 receptor stimulation. 38 Collectively, these findings outline the considerable influence of CB1 signaling in the midbrain and limbic sites of food motivation. By regulating feeding behavior through signaling in the hypothalamus, midbrain, limbic and hindbrain sites, the endocannabinoid system provides a common link in a diverse network controlling food intake.…”

mentioning

confidence: 89%

Neurosystems linking corticolimbic and hypothalamic pathways in energy balance: view from the Chair

Fulton

2009

Int J Obes

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Recent work has advanced our knowledge of the neural pathways interfacing corticolimbic substrates of food motivation and reward with hypothalamic controls of food intake. As a neuroanatomical interface between limbic motivational processes, energy-sensing mechanisms in the mediobasal hypothalamus and motor output pathways, several studies draw attention to the lateral hypothalamus. Reviewed here are some highlights of the first session of the 11th International Symposium of the Merck- Keywords: dopamine; endocannabinoids; nucleus accumbens; orexin; melanin-concentrating hormoneThe central nervous system plays a crucial role in integrating numerous hormonal and metabolic signals derived from the periphery and thereby generating adaptive behavioral responses to changing energy demands. Under normal conditions, there are several mechanisms at the level of the hypothalamus and hindbrain that effectively respond to states of energy deficit or surplus in part by modulating appetite. The significance of key hypothalamic neuronal populations for energy homeostasis is underscored by genetic gain-and loss-function studies. 1 On the other hand, there exist cortical and limbic processes that underlie the cognitive and rewarding aspects of food by assimilating information about taste, texture, smell and post-ingestive consequences. 2,3 Sensory and value representations of food and the cues and properties associated with obtaining food are stored in the memory where they serve an essential function, especially during conditions of low food availability, to orient animals back to (or away from in conditions of aversion) the source of food.The heightened behavioral, emotional and cognitive response to palatable high-fat and -sugar foods that has evolved can be understood in terms of what these foods offer in energy value. Indeed, the rewarding experience that is produced by eating tasty, energy-rich foods can produce a lasting impression that acts to strengthen action-outcome associations and reinforce future behavior directed at obtaining food. Of relevance for the epidemiology of obesity in humans, we must consider that food intake is accompanied by several precipitating factors in modern industrialized societies. Many foods come in catchy packaging, are well advertised, easily obtainable and relatively cheap. Thus, we are frequently bombarded with food-associated cues that remind us about how, where and when we can get access to these foods. As we have become well acquainted with the contribution of rewarding, easily accessible and inexpensive high-fat and -sugar foods to the epidemic of obesity, it is increasingly evident that we need to unravel the neural mechanisms that process not only the hedonic effects of palatable foods, but also those that govern reward-relevant learning, valuation and decision making in the context of modern social and economic climates.Of direct bearing to the discussion here, it is important that we identify which neural pathways and processes interface corticolimbic mechanisms affecting feeding...

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“…CB1 receptors are highly expressed in the above areas involved in reward thus indicating that the cannabinoid system is directly involved in feeding behavior [49][50][51][52][53][54].…”

Section: Cannabinoids and Eating Disordersmentioning

confidence: 99%

The role of endocannabinoids in the control of eating disorders

Milano¹,

Tecce²,

Capasso³

2017

Dis Disord

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Eating Disorder (ED) is a syndrome characterized by persistent alteration of eating behavior and the conditions that cause an insufficient ingestion and/or adsorption of foods. There are three different ED diseases: Anorexia Nervosa (AN), Bulimia Nervosa (BN) and Binge Eating Disorders (BED). ED are complex conditions that arise from a combination of long-standing behavioral, emotional, psychological, interpersonal, and social factors. The neuronal circuits that control the ingestion of food are mainly related to catecholaminergic, serotoninergic and peptidergic systems. In this respect, while serotonin, dopamine and prostaglandin promote the ingestion of food, by contrast, neuropeptide Y, norepinephrine, GABA and opioid peptides inhibit food ingestion thus causing the occurrence of ED. The drugs mainly used in the treatment of ED are antidepressants such as selective serotonin reuptake inhibitors and tricyclic antidepressant. Additionally, mood stabilizers (lithium), anxiolytics, serotonin and noradrenalin reuptake inhibitors and antipsychotic drugs are often used in the treatment of ED.Several studies indicate that the endocannabinoid system is involved in ED supporting the idea that the cannabinoid signaling system is a key modulatory element in the activity in the brain area associated with ED.

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Increased motivation for beer in rats following administration of a cannabinoid CB1 receptor agonist

Cited by 219 publications

References 30 publications

Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat

Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat

Neurosystems linking corticolimbic and hypothalamic pathways in energy balance: view from the Chair

The role of endocannabinoids in the control of eating disorders

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