Cannabinoid Conditioned Reward and Aversion: Behavioral and Neural Processes (original) (raw)
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A behavioural model to reveal place preference to Δ9-tetrahydrocannabinol in mice
Psychopharmacology, 2000
Rationale: The rewarding properties of Δ9- tetrahydrocannabinol (THC) are difficult to demonstrate in rodents using standard procedures. Objective: To evaluate the motivational responses of THC in the place conditioning paradigm in mice after minimizing the dysphoric effects of the first drug exposure and/or the consequences of its pharmacokinetic properties. Methods: Mice were conditioned to THC (1 or 5 mg/kg) using an unbiased procedure with an elevated number of pairings and long conditioning time. Results: A place aversion was observed with 5 mg/kg THC using a standard protocol. Similar results were obtained when the CB-1 receptor antagonist SR 141716A (1 mg/kg) was administered immediately after each THC conditioning period. However, mice receiving a priming THC injection and conditioned 24 h later showed a place preference with 1 mg/kg THC and no effect with 5 mg/kg THC. Conclusion: THC produces a clear place preference in mice by using a long period of conditioning and avoiding the possible dysphoric consequences of the first drug exposure.
…, 2004
Rationale: Using the place-preference conditioning paradigm, we evaluated the potential of the two most prominent cannabinoids found in marijuana, the psychoactive component D 9 -tetrahydrocannabinol (D 9 -THC) and the nonpsychoactive component cannabidiol (CBD), to potentiate extinction of a cocaine-induced and an amphetamine-induced conditioned place preference in rats. Methods: To determine the effects of pretreatment with D 9 -THC or CBD on extinction, a cocaine-induced and amphetamine-induced place preference was first established. Rats were then given an extinction trial, during which they were confined to the treatment-paired floor for 15 min. Thirty minutes prior to the extinction trial, they were injected with a low dose of D 9 -THC (0.5 mg/kg), CBD (5 mg/kg) or vehicle. The potential of the CB 1 receptor antagonist, SR141716, to reverse the effects of D 9 -THC or CBD was also evaluated. To determine the hedonic effects of CBD, one distinctive floor was paired with CBD (5 mg/kg) and another with saline. Finally, to determine the effect of D 9 -THC or CBD on the establishment and/or the expression of a place preference during four cycles of conditioning trials, rats were injected with D 9 -THC (0.25-1 mg/kg), CBD (5 mg/kg) or vehicle 25 min prior to receiving an injection of amphetamine followed by placement on the treatment floor; on alternate days, they received injections of vehicle followed by saline and placement on the nontreatment floor. The rats then received two test trials; on one trial they were pretreated with the cannabinoid and on the other trial with vehicle. Results: D 9 -THC and CBD potentiated the extinction of both cocaine-induced and amphetamine-induced conditioned place preference learning, and this effect was not reversed by SR141716. The cannabinoids did not affect learning or retrieval, and CBD was not hedonic on its own. Conclusions: These results are the first to show that both D 9 -THC, which acts on both CB1 and CB2 receptors, and CBD, which does not bind to CB 1 or CB 2 receptors, potentiate the extinction of conditioned incentive learning.
Endogenous cannabinoids as an aversive or counter-rewarding system in the rat
Neuroscience Letters, 1997
Human use of marijuana (Cannabis sativa) is widely assumed to have rewarding properties, a notion supported by its widespread recreational use. However, no study has clearly demonstrated such effects in animal models. The purpose of this study was to test for the presumed rewarding effect of cannabinoids using a conditioned place preference paradigm. The results showed that animals failed to develop place conditioning at a low dose (1.5 mg/kg) and developed a place aversion at a high dose (15 mg/kg) of the active principle in marijuana, D 9 -tetrahydrocannabinol (D 9 -THC), a finding consistent with most previous studies. Moreover, the administration of the cannabinoid antagonist SR141716A induced a conditioned place preference at both a low (0.5 mg/kg) and a high (5 mg/kg) dose. In summary, cannabinoid antagonism produced place preference while cannabinoid agonism induced place aversion. These results suggest that endogenous cannabinoids serve normally to suppress reward or to induce aversion.
Pharmacology Biochemistry and Behavior, 1990
Using antagonists to assess neurochemical coding of a drug's ability to establish a conditioned place preference. PHARMACOL BIOCHEM BEHAV 37(3) [425][426][427][428][429][430][431] 1990.--Rats were given morphine as an agent of putative conditioning to establish a place preference. Doses of 4 and 8 mg/kg of morphine did establish reliable conditioned place preferences (CPP's). Other rats were given one of the doses of morphine and one of a number of antagonists in procedures designed to assess which antagonists would specifically block morphine's ability to establish a CPP indicative of positivity. Doses of naloxone and larger doses of naltrexone but not smaller ones did antagonize morphine's effects. A dose of the benzodiazepine antagonist Ro 15-1788 did not attenuate morphine's effects. It was concluded that morphine's positivity is dependent upon actions by way of receptors sensitive to naloxone and naltrexone, but that morphine's positivity is less sensitive to naltrexone's effects than morphine's analgesia.
Highway to hell or magic smoke? The dose-dependence of Δ9-THC in place conditioning paradigms
Learning & Memory
The prerequisites for responsible cannabis use are at the heart of current inquiries into cannabis decriminalization by policy makers as well as academic and nonacademic stakeholders at a global scale. Δ9-tetrahydrocannabinol (Δ9-THC), the prime psychoactive compound of the cannabis sativa, as well as cannabimimetics that resemble the pharmacological properties and psychological effects of Δ9-THC, lend themselves handsomely to the preclinical scrutiny of reward-related behavior because they carry marked translational value. Although a functional dichotomy of the psychological effects of Δ9-THC (rewarding versus aversive) has been abundantly reported in place conditioning (PC) paradigms, and might be best attributed to a dose-dependence of Δ9-THC, most PC studies with Δ9-THC feature no significant effects at all. Therefore, after decades of rigorous research, it still remains undetermined whether Δ9-THC generally exerts rewarding or aversive effects in rodents. Here, we set out to ex...
Acute blockade of CB1 receptor leads to reinstatement of MDMA-induced conditioned place preference
Pharmacology Biochemistry and Behavior, 2011
Cannabis is one of the drugs most commonly consumed in combination with ecstasy (3,4-methylenedioxymethamphetamine, MDMA). Although numerous studies have attempted to further our understanding of the role of the cannabinoid system in drug abuse, few have focused on how it influences the rewarding effects of MDMA. The aim of the present study was to evaluate the role of the CB1 cannabinoid receptor in vulnerability to reinstatement of a MDMA-induced conditioned place preference (CPP). Mice were first conditioned with 5 mg/kg of MDMA. Once the preference had been extinguished, a priming dose of MDMA, alone or plus the CB1 cannabinoid agonist WIN 55,212-2 (0.1 and 0.5 mg/kg) or the CB1 cannabinoid antagonist SR 141716A (0.3 mg/kg), was administered on alternate days. The CB1 receptor antagonist, alone or with any of the priming doses of MDMA, induced reinstatement of the preference. In contrast, WIN 55,212-2 had no effect on reinstatement of the MDMA-induced CPP when administered alone, but potentiated the effects of subthreshold priming doses of MDMA. These results highlight the important role of the CB1 receptor in vulnerability to reinstatement of drug-seeking behavior and point to the importance of the endocannabinoid system in the addictive potential of MDMA.
Behavioural Pharmacology, 2007
Data on the ability of D 9 -tetrahydrocannabinol (THC) to modify reward processes in experimental animals are inconsistent. This study examined the effects of D 9 -THC on brain reward function using the rate-frequency curve shift paradigm of intracranial self-stimulation (ICSS) and the conditioned place preference (CPP) paradigm. In ICSS tests, rats were implanted with electrodes into the medial forebrain bundle. After brain stimulation reward thresholds stabilized, rats received intraperitoneal injections of D 9 -THC (0, 0.5, 1 and 2 mg/kg) or the CB 1 receptor antagonist SR141716A (0, 0.02 mg/kg) and D 9 -THC (0, 2 mg/kg). The two highest doses of D 9 -THC significantly increased the threshold ICSS frequency. SR141716A reversed the action of D 9 -THC (2 mg/kg), without affecting reward thresholds by itself. In the CPP test, mice received intraperitoneal injections of D 9 -THC (0, 1 or 3 mg/kg). D 9 -THC showed neither statistically significant preference nor aversion in either of the doses tested. These findings indicate that D 9 -THC, in contrast to other drugs of abuse, does not facilitate ICSS or support CPP under the present experimental conditions, but rather has a dose-dependent inhibitory influence on ICSS.