Tramadol and Tapentadol Induce Conditioned Place Preference with a Differential Impact on Rewarding Memory and Incubation of Craving

Abstract

Tramadol and tapentadol, synthetic opioids commonly prescribed for moderate-to-severe pain, have a unique pharmacology that optimizes their analgesia and safety. However, they are not devoid of risks, presenting addictive, abuse, and dependence potential. While tramadol-reinforcing properties have been documented by various studies with human and animal models, including conditioned place preference (CPP) assays, no similar studies have been performed with tapentadol. In the present study, we performed CPP assays by intraperitoneally administering Wistar rats with a tramadol/tapentadol therapeutic dose. Animal permanence and the number of entries in the CPP compartments were recorded in the preconditioning phase and then 1 (T1), 7 (T7), and 14 (T14) days after conditioning. Both opioids induced a change in place preference (T1), suggesting that they have short-term reinforcing properties. However, only tramadol was associated with place preference retention (T7 and T14), with an increase in the number of entries in the opioid-paired compartment (T1 and T7), showing that it causes rewarding memory and incubation of craving. The results indicate that at therapeutic doses: (1) both drugs cause short-term rewarding effects and (2) as opposed to tramadol, tapentadol does not cause CPP retention, despite its higher central nervous system activity and stricter scheduling.

Tramadol Abuse Among Yeloyelo Drivers in the Tamale Metropolis

“…Perananthan & Buckley, (11) works supported this nding and equally reported that users of tramadol sometimes grind the pills into tiny pieces to lick ("snorting"). Furthermore, Barbosa et al (19)agreed with this observation, and reported that licking was widespread due to the expected impact of doing so (noting the quick high, and feeling good). He found that nearly half (44%) of the participants "Always" stripped away foreign matter before licking, citing equal frequency either a desire for only the drug in the powder for a more immediate high (16%) or a dislike of the shell's properties, such as being sticky, irksome or scorching the nose, or experiencing dust in the nose (16%).…”

“…The study also agrees with a study in Egypt about the causes of addiction, it was reported that, 50% of the participants studied were addicted as a result of peer in uence. Agani, in Saudi Arabia, it was reported that tramadol dependence began as a result of users acting under the in uence of their friends (19).…”

“…Interestingly, tramadol together with some other opioids may have pharmacokinetic and pharmacodynamic interactions that increase their toxicity and lead to death (18), tramadol is a mild opioid with a pharmacological effect comparable to codeine, its use has a possibility of tramadol addiction (4) (8). as such it has a major adverse effects such as psychotic convulsions and deadly overdoses (19).…”

An Update on Psychoactive Substances: Pharmacology and Toxicology Issues

“…The six published articles highlight different aspects of the pharmacology and toxicology of several psychotropics; most of them are represented by opiates/opioids, e.g., tramadol [ 4 , 5 ], tapentadol [ 4 ], and fentanyl [ 6 ], but other categories here mentioned are selective serotonin reuptake inhibitor (SSRI) antidepressants [ 7 ], new psychoactive substances (NPSs) known as cathinones [ 8 ], and the hallucinogen drug psilocybin [ 9 ].…”

“…The first paper [ 4 ] aimed to comparatively assess the rewarding and reinforcing properties of the synthetic opioids tramadol and tapentadol, at a therapeutic dose; the conditioned place preference (CPP) assay, a non-clinical animal paradigm of addiction potential in rats, was used. Both opioids showed short-term reinforcing properties; however, only tramadol showed the potential to induce drug memory and the incubation of craving several days after the last drug administration, suggesting that tapentadol has a lower propensity to induce dependence than tramadol.…”