Table 4.
Studies related to the rewarding properties of cannabimimetics.
| Substance | Dosage Regimen | Studies | References |
|---|---|---|---|
| WIN 55212-2 | Intravenous self-administration model in drug-naive mice of WIN 55212-2 (0.5 and 0.1 mg/kg per injection) | WIN 55,212-2 was intravenously self-administered by mice in a concentration-dependent manner according to a bell-shaped curve | Martellotta et al., 1998 |
| HU210 | Conditioned place preference (CPP) in male rats: HU210 (20, 60 and 100 μg/kg), and Δ9-THC (1.5 mg/kg) | HU210 and Δ9-THC produced aversion as expressed by time spent in the drug-paired compartment of the CPP apparatus | Cheer et al., 2000 |
| WIN 55212-2 | Intravenous SA in rats WIN 55,212-2 at doses ranging from 6.25 to 50 μg/kg per injection, under a fixed-ratio 1 (FR1) schedule of reinforcement and nose-pokes as the operant responses | Response rate depended on the drug dose available, with maximum rates occurring at 12.5 microg/kg per injection | Fattore et al., 2001 |
| WIN 55212-2 | Fast-scan cyclic voltammetry: systemic administration at a dose of 125 μg/kg | WIN55,212–2 enhances dopamine transients but depresses electrically evoked release | Cheer et al., 2004 |
| WIN 55212-2 CP 55940 HU-210 |
After Intracranial self-stimulation (ICSS) of the medial forebrain bundle, rats received intraperitoneal injections of WIN 55,212-2 (graded doses 0.1, 0.3, 1 and 3 mg/kg), CP 55,940 (graded doses 10, 30, 56 and 100 μg/kg), or HU-210 (graded doses 10, 30, 100 μg/kg) | With the exception of the highest dose of all cannabinoid agonists tested, which significantly increased the threshold frequency required for ICSS into the medial forebrain bundle, all other doses of the tested drugs did not affect ICSS thresholds. The CB1 receptor antagonist SR141716A reversed the actions of WIN 55,212-2 and CP 55,940, but not HU-210 | Vlachou et al., 2005 |
| WIN 55212-2 | Intravenous self-administration (SA). Rats, trained for 3 weeks to self-administer WIN 55,212-2 (12.5 μg/kg) in single daily 1-h sessions under a fixed ratio 1 (FR 1) schedule, then switched to FR 2 for a further week. During SA sessions, microdialysis assays were performed every 3rd day, and then daily starting from the 13th session. Dialysate DA from the NAc shell and core was monitored before, during, and for 30 min after SA | Response-contingent WIN 55,212-2 SA preferentially increases the NAc shell DA output as compared to that of the core independently from the duration of the WIN 55,212-2 exposure. Increase in NAc DA is strictly related to WIN 55,212-2 actions because it is not observed during extinction despite active responding | Lecca et al., 2006 |
| WIN 55212-2 | Rats received intraperitoneal injections of WIN55,212-2 (0.1, 0.3 or 1 mg/kg) for 20 subsequent days. Thresholds for ICSS were measured before and after each injection | WIN55,212-2 (1 mg/kg) significantly increased ICSS thresholds from the first day of administration, an effect that remained stable across the subsequent days of administration. These findings indicate that repeated WIN55,212-2 administration elicited a sustained increase in ICSS | Mavrikaki et al., 2010 |
| JWH-018 JWH-073 JWH-210 |
Adult male rats trained to discriminate 3 mg/kg Δ(9)-THC or 0.3 mg/kg JWH-018 from vehicle | JWH-018, JWH-073, and JWH-210 fully substituted in Δ(9)-THC-trained rats and Δ(9)-THC substituted in JWH-018-trained rats | Wiley et al., 2014 |
| JWH-018 JWH-073 JWH-250 JWH-200 JWH-203 AM-2201 CP 47,497-C8-homolog |
These compounds were then tested for substitution in rats trained to discriminate Δ-THC (3 mg/kg, intraperitoneally) | Each of the compounds fully substituted for the discriminative stimulus effects of Δ-THC, mostly at doses that produced only marginal amounts of rate suppression. JWH-250 and CP 47,497-C8-homolog suppressed response rates at doses that fully substituted for Δ-THC | Gatch and Forster, 2014 |
| CP 55940 | Acute and repeated administration (7 days) of CP55,940 (0.12-0.18)mg/kg).on operant responding for electrical brain stimulation of the medial forebrain bundle in C57BL/6J mice | CP55,940 attenuated ICSS in a dose-related manner. This effect was blocked by the CB1 receptor antagonist rimonabant | Grim et al., 2015 |
| JWH-018 | Microdialysis studies in rats: 0.125 mg/kg ip 0. 25 mg/kg ip 0. 5 mg/kg ip Rats self-administered JWH-018 (20 μg/kg/infusion) in single daily 1 h FR3 sessions. C57BL/6 mice self-administered JWH-018 (30 μg/kg/infusion) in single daily 2 h FR1 sessions | JWH-018 0.25 mg/kg ip increases dopamine transmission in Nac shell, but not in NAc core nor in mPFC. The lower and the higher doses do not stimulate DA transmission so the dose-response curve of this compound has an inverted U-shape. Both rats and mice readily acquired two different operant behaviors: nose-poking into an optical switch (rats) and lever-pressing (mice) | De Luca et al., 2015a |
| BB-22 5F-PB-22 5F-AKB-48 STS-135 |
Microdialysis studies in rats: BB-22 (0.003-0.01 mg/kg i.v.) 5F-PB-22 (0.01 mg/kg i.v.) 5F-AKB-48 (0.1 mg/kg i.v.) STS-135(0.15 mg/kg i.v.) | BB-22 (0.003-0.01 mg/kg i.v.) increased dialysate DA in the accumbens shell but not in the core or in the medial prefrontal cortex, with bell shaped dose-response curve and an effect at 0.01 mg/kg and a biphasic time-course; systemic AM251 (1.0 mg/kg i.p.) completely prevented the stimulant effect of BB-22 on dialysate DA in the NAc shell. All the other compounds increased dialysate DA in the NAc shell at doses consistent with their in vitro affinity | De Luca et al., 2015b |