Endogenous cannabinoids are not involved in cocaine reinforcement and development of cocaine-induced behavioural sensitization
Introduction
The endogenous cannabinoid system consists of cannabinoid type 1 receptors (CB1), CB2 receptors, which are restricted to the periphery, and the endogenous cannabinoids anandamide and 2-arachidonyl glycerol (2-AG) (Childers and Breivogel, 1998). Cannabinoid CB1 receptors have been implicated in the rewarding aspects not only of the Cannabis sativa-derived compound Δ9-tetrahydrocannabinol (Δ9-THC) (Maldonado and Rodriguez, 2002), but also of opiates such as heroin and morphine Chaperon et al., 1998, Navarro et al., 2001, Solinas et al., 2003, De Vries et al., 2003. Moreover, endogenous cannabinoids may be involved in reward-related effects of other drugs of abuse such as alcohol (Arnone et al., 1997, Gallate and McGregor, 1999, Serra et al., 2001, Lallemand et al., 2001, Freedland et al., 2001 but Vacca et al., 2002, Colombo et al., 2002, Wang et al., 2003), nicotine (Cohen et al., 2002), 3,4-methylenedioxymethamphetamine (MDMA) (Braida and Sala, 2002) and cocaine (Chaperon et al., 1998, De Vries et al., 2001 but Fattore et al., 1999).
Here we further investigated the role of CB1 receptors in acute and chronic reward-related effects of cocaine. For this purpose, we used the selective CB1 receptor antagonist SR141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazole-3-carboxyamide hydrochloride (Rinaldi-Carmona et al., 1995). First, the involvement of CB1 receptors in the initiation of intravenous cocaine self-administration in drug-naive mice was studied. Initiation of cocaine self-administration is predominantly determined by the positive reinforcing properties of cocaine and is not or less influenced by effects of repeated drug administration (Van Ree et al., 1999). In a yoked-controlled self-administration paradigm, the effects of acute CB1 receptor blockade with SR141716A upon cocaine reinforcement were determined. In the second part of this study, the involvement of CB1 receptors in chronic effects of cocaine was determined. Prolonged exposure to cocaine, or other drugs of abuse, leads to sensitization of brain systems, which mediate incentive salience or ‘drug wanting’ (Robinson and Berridge, 2000). Here behavioural sensitization to the locomotor stimulant effects of cocaine, which is assumed to involve the same neural substrates, was studied for involvement of CB1 receptors. SR141716A or placebo was co-administered with repeated intermittent cocaine or saline sensitization injections for 11 subsequent days.
Section snippets
Animals
Male C57Bl/6Jico mice (Charles River, l'Arbresle, France) aged 2–3 months were group-housed (2–4) in extended Macrolon© type I cages with water and food pellets available ad libitum. Environmental conditions were controlled (22 °C and 50% humidity; lights on at 7:00 a.m. and lights off at 7:00 p.m., GDL Utrecht University). The experimental procedures were approved by the Ethical Committee for Animal Experiments of the University Medical Center Utrecht.
Effects of SR141716A upon intravenous cocaine self-administration
This experiment was designed to determine
Effects of SR141716A upon intravenous cocaine self-administration
Overall analysis of the nose pokes during the 10-min pre-test revealed no effect of SR141716A treatment nor were there differences between active and yoked control mice or between cocaine doses (Table 1), showing that during the initial pre-test all mice were equally active in their nose poke responding.
During the cocaine self-administration session, the active mice responded with significantly more nose pokes than the yoked control mice did (Fig. 1A, overall analysis, effect of type F
Discussion
Endogenous cannabinoid systems have been implicated in the rewarding aspects not only of the C. sativa derived compound Δ9-tetrahydrocannabinol (Δ9-THC), but also of opiates, alcohol and psychostimulants. Here we investigated the involvement of cannabinoid CB1 receptors in cocaine reinforcement and cocaine-induced behavioural sensitization. Neither cocaine self-administration in drug-naive mice nor cocaine-induced behavioural sensitization was affected by co-administration of the CB1 receptor
Acknowledgements
This work is supported by the Netherlands Organisation for Scientific Research (ZON-MW grant 985-01-004). Sanofi-synthelabo Recherche (Montpellier, France) kindly provided a sample of the CB1 antagonist SR141716A, which is gratefully acknowledged.
References (33)
- et al.
Conditioned place preference induced by the cannabinoid agonist CP 55,940: interaction with the opioid system
Neuroscience
(2001) - et al.
Cannabis and endogenous cannabinoid systems
Drug Alcohol Depend
(1998) - et al.
Cannabinoid CB(1) receptor knockout mice fail to self-administer morphine but not other drugs of abuse
Behav. Brain Res
(2001) - et al.
CB1 cannabinoid receptor agonist WIN 55,212-2 decreases intravenous cocaine self-administration in rats
Behav. Brain Res
(1999) - et al.
Kappa-opioid receptor agonist U50,488H modulates cocaine and morphine self-administration in drug-naive rats and mice
Eur. J. Pharmacol
(1997) - et al.
Pre-exposure to the cannabinoid receptor agonist CP 55,940 enhances morphine behavioral sensitization and alters morphine self-administration in Lewis rats
Eur. J. Pharmacol
(2003) - et al.
Overeating, alcohol and sucrose consumption decrease in CB1 receptor deleted mice
Neurosci. Lett
(2003) - et al.
Conditioned place preference to morphine in cannabinoid CB1 receptor knockout mice
Brain Res
(2002) - et al.
Biochemical and pharmacological characterisation of SR141716A, the first potent and selective brain cannabinoid receptor antagonist
Life Sci
(1995) - et al.
The cannabinoid receptor antagonist SR 141716 prevents acquisition of drinking behavior in alcohol-preferring rats
Eur. J. Pharmacol
(2001)
Boosting effect of morphine on alcohol drinking is suppressed not only by naloxone but also by the cannabinoid CB(1) receptor antagonist, SR 141716
Eur. J. Pharmacol
Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of central cannabinoid (CB1) receptors
Psychopharmacology (Berlin)
Role of the endocannabinoid system in MDMA intracerebral self-administration in rats
Br. J. Pharmacol
Involvement of central cannabinoid (CB1) receptors in the establishment of place conditioning in rats
Psychopharmacology (Berlin)
SR141716, a central cannabinoid (CB(1)) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats
Behav. Pharmacol
Stimulation of voluntary ethanol intake by cannabinoid receptor agonists in ethanol-preferring sP rats
Psychopharmacology (Berlin)
Cited by (76)
Sex differences in cocaine-associated memory: The interplay between CB<inf>1</inf>, mGluR5, and estradiol
2021, PsychoneuroendocrinologyCitation Excerpt :First, accrued evidence suggests that CB1 receptors modulate the primary rewarding effects of several drugs of abuse (e.g., cannabinoids, nicotine, alcohol, and opioids) but not that of cocaine (Maldonado et al., 2006). For example, Rim does not affect cocaine self-administration (Caille et al., 2007; Caille and Parsons, 2006; Fattore et al., 2007; Filip et al., 2006; Tanda et al., 2000), and the CB1 KO mice express normal cocaine-induced CPP and self-administration (Cossu et al., 2001; Houchi et al., 2005; Lesscher et al., 2005; Martin et al., 2000). On the other hand, CB1 receptors mediate cocaine-associated memory underpinning the persistence (relapse) of cocaine addiction.
Role of the endocannabinoid system in drug addiction
2018, Biochemical PharmacologyThe Role of the Endocannabinoid System in Addiction
2017, The Endocannabinoid System: Genetics, Biochemistry, Brain Disorders, and TherapyOn the Role of the Endocannabinoid System in Cocaine Addiction
2016, Neuropathology of Drug Addictions and Substance MisuseOn the Role of the Endocannabinoid System in Cocaine Addiction
2016, Neuropathology of Drug Addictions and Substance Misuse Volume 2: Stimulants, Club and Dissociative Drugs, Hallucinogens, Steroids, Inhalants and International AspectsChanges in endocannabinoid and N-acylethanolamine levels in rat brain structures following cocaine self-administration and extinction training
2014, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :In contrast, cocaine self-administration and withdrawal resulted in long-lasting CB1 receptor up-regulation in many brain structures (Adamczyk et al., 2012a). Acute pharmacological blockade of CB1 receptors either reduced (Li et al., 2009; Soria et al., 2005; Xi et al., 2008) or did not change the rewarding properties of cocaine (Adamczyk et al., 2012b; Lesscher et al., 2005; Orio et al., 2009). The constitutive activation of CB1 receptors was associated with the external cues associated with cocaine that appeared during conditioned locomotion or drug-seeking behaviour (Adamczyk et al., 2012b; de Vries et al., 2001; Gerdeman et al., 2008).