Original articleDiscriminative stimulus properties of dextromethorphan in rats
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Assessment of the rapid and sustained antidepressant-like effects of dextromethorphan in mice
2020, Pharmacology Biochemistry and BehaviorCitation Excerpt :However, DM abuse (“Robotripping”) has been well documented at doses significantly higher than the antidepressant dose (30–45 mg vs. 200–1500 mg) (Antoniou and Juurlink, 2014; Boyer, 2004; Falck et al., 2006). Preclinical animal studies have found that DM produces a place preference and shares discriminative stimulus properties with the noncompetitive NMDA receptor antagonists PCP and dizocilpine (MK-801) (Gavend et al., 1995; Holtzman, 1994; Shin et al., 2005). Interestingly, the abuse-related effects found in preclinical studies are at the same doses (30 mg/kg) that produce the antidepressant-like effects.
Dextromethorphan-induced psychotoxic behaviors cause sexual dysfunction in male mice via stimulation of σ-1 receptors
2012, Neurochemistry InternationalCitation Excerpt :Nevertheless, there are several concerns about use of DM because numerous cases of abuse, including drug-seeking behavior, have been reported globally since the 1960s (Chung et al., 2004; McCarthy, 1971; Murray and Brewerton, 1993; Noonan et al., 2000; Rammer et al., 1988; Schwartz, 2005; Wolfe and Caravati, 1995). DM is primarily metabolized in vivo to dextrorphan (DX) by O-demethylation (Schadel et al., 1995); however, we and others have reported that DX is not essential for the neuroprotective action, and DM itself has effects (Gavend et al., 1995; Kim et al., 2003a; Tortella et al., 1989). DM has a higher affinity than DX at [3H] DM binding sites (presumably sigma (σ) sites) but has a lower affinity than DX at DX binding sites (presumably phencyclidine (PCP) sites (Craviso and Musacchio, 1983; Shin et al., 2011, 2010, 2008; Tortella et al., 1989).
Social reward-conditioned place preference: A model revealing an interaction between cocaine and social context rewards in rats
2008, Drug and Alcohol DependenceCitation Excerpt :Additionally, the results of Experiments 6 and 7 suggest that it is the rewarding effects of cocaine, rather than non-specific psychoactive stimulus effects, that mediate the enhancement of social reward-CPP. Specifically, we demonstrated that dextromethorphan failed to interact with social reward to produce a CPP despite its ability to produce discriminative stimulus effects (Holtzman, 1994; Gavend et al., 1995) and the present findings that it attenuated play behaviors and locomotor activity. Further research is needed to draw firm conclusions regarding the precise nature of the interaction between drug and social rewards; however in any case, these findings have important implications for understanding drug abuse given that many adolescents first begin to experiment with drugs while in a social setting.
Comparative effects of dextromethorphan and dextrorphan on nicotine discrimination in rats
2006, Pharmacology Biochemistry and BehaviorA role for sigma receptors in stimulant self administration and addiction
2011, PharmaceuticalsComparison of the Effects of Dextromethorphan, Dextrorphan, and Levorphanol on the Hypothalamo-Pituitary-Adrenal Axis
2004, Journal of Pharmacology and Experimental Therapeutics