The 5-HT6 serotonin receptor antagonist SB-271046 attenuates the development and expression of nicotine-induced locomotor sensitisation in Wistar rats

Psychostimulants

“…The first report that 5-HT 6 receptors were of relevant demonstrated that augmented accumbal expression of 5-HT 6 receptors blocked the rewarding, but not psychomotor actions of cocaine (Ferguson, Mitchell, & Neumaier, 2008). There is evidence that application of 5-HT 6 receptor antagonists reduced the development and expression of nicotine-induced behavioral sensitization (de Bruin, Kloeze, & McCreary, 2011), reduced ethanol and nicotine seeking (de Bruin et al, 2013), altered cocaine, maintained self-administration, and reinstated cocaine-seeking behavior and the expression of conditioned place preference (Fijał et al, 2010;van Gaalen, Schetters, Schoffelmeer, & De Vries, 2010).…”

N′-(Arylsulfonyl)pyrazoline-1-carboxamidines as Novel, Neutral 5-Hydroxytryptamine 6 Receptor (5-HT6R) Antagonists with Unique Structural Features

“…Following the same procedure as described for 1, reaction of 63ak (380 mg, 0.97 mmol) with ethylamine (1 mL of a 70% solution in water, excess) gave 390 mg (100%) of 36 as a yellow oil. 1 H NMR (400 MHz, CDCl 3 ) δ 0.96 (t, J = 7.5 Hz, 3H), 1.17 N 0 -(5-Chlorothiophen-2-ylsulfonyl)-N,4-diethyl-4,5-dihydro-1H-pyrazole-1-carboxamidine (37). By the use of 5-chlorothiophene-2-sulfonyl chloride as reagent in the general procedure described above and subsequent reverse phase preparative HPLC purification, 82 mg (24%) of 37 was isolated.…”

“…Adjunctive therapy with 5-HT 6 R antagonists in schizophrenia may have additional benefits beyond cognition. First, schizophrenic patients are known to be more prone to addiction, and 5-HT 6 R antagonism has been shown to be associated with antiaddictive behavior in several studies. − Second, atypical antipsychotics are frequently associated with body weight gain, and 5-HT 6 R modulators have been shown to reduce food intake and body weight in diet-induced obese rodent models, presumably through a centrally mediated effect on satiety. , …”

Nicotine‐induced locomotor sensitization: pharmacological analyses with candidate smoking cessation aids

“…Following chronic‐intermittent administration sensitization to these latter effects are observed (O'Neill, Dourish & Iversen ; Domino ; Miller et al . ; Palmatier & Bevins ; Le Foll & Goldberg ; Akdag, Kayir & Uzbay ; de Bruin, Kloeze & McCreary ; Goutier, Kloeze & McCreary ). Behavioral sensitization to the psychomotor actions of nicotine involves the progressive increase in the locomotor activity response following repeated intermittent exposure and has been proposed to model the addiction and relapse processes observed in humans (Robinson & Berridge , ; Miller et al .…”