Stimulus properties of antidepressants in the rat

Abstract

Various doses of bupropion HCl (Wellbatrin) (5, 10, and 20 mg/kg), a new phenylaminoketone antidepressant, were employed as cues in a two-lever operant discrimination from saline control injections in rats on an FR10 schedule of food reinforcement. Subjects reached and maintained a high level of discrimination in the O vs 20 mg/kg bupropion stimulus condition but not at the lower doses. In generalization testing, the following compounds produced dose-related responding on the bupropion lever: viloxazine, nomifensine, caffeine, d-amphetamine, cocaine, methylphenidate, and benzylpiperazine. Drugs that failed to show dose-related generalization included phenethylamine, thyrotropin-releasing hormone, imipramine, nortriptyline, amitriptyline, desipramine, mianserin, chlordiazepoxide, diazepam, scopolamine, phenobarbital, and morphine. With the important exception of viloxazine, the generalization profile of bupropion seems to reflect its previously reported locomotor stimulant effects in the rat rather than its antidepressant activity and suggests that species differences exist between man and rat with regard to the pharmacologic activity of this new antidepressant.

N-Substituted Piperazines Abused by Humans Mimic the Molecular Mechanism of 3,4-Methylenedioxymethamphetamine (MDMA, or ‘Ecstasy’)

“…It is noteworthy that the amount of forward locomotion produced by BZP was much greater than locomotion produced by MDMA. Our behavioral findings with BZP support previous results demonstrating this drug has amphetamine-like properties in rats (Jones et al, 1980) and humans (Bye et al, 1973). Based on the predominant effects of BZP on extracellular DA, it appears that stimulation of DA transmission may underlie the ability of this drug to induce amphetamine-like ambulation and stereotypy (see Kelly and Iversen, 1976;Kuczenski and Segal, 1994).…”

“…Similar to MDMA, however, TFMPP displays presynaptic actions that include stimulation of SERT-mediated 5-HT release from neurons, as demonstrated in vitro (Pettibone and Williams, 1984) and in vivo (Auerbach et al, 1991). There is limited information available on the molecular mechanism of BZP, but this drug elicits amphetamine-like behavioral effects in rodents (Jones et al, 1980) and humans (Bye et al, 1973). No scientific investigations regarding the neurobiology of BZP plus TFMPP (BZP/TFMPP) are available.…”

Selective Suppression of Cocaine- versus Food-Maintained Responding by Monoamine Releasers in Rhesus Monkeys: Benzylpiperazine, (+)Phenmetrazine, and 4-Benzylpiperidine

“…Regarding benzylpiperazine, both cocaine and benzylpiperazine substituted for the discriminative stimulus effects of bupropion in rats (Jones et al, 1980), and like cocaine, benzylpiperazine produced amphetamine-like discriminative stimulus effects and maintained drug self-administration in rhesus monkeys (Fantegrossi et al, 2005). In humans, benzylpiperazine has emerged as a drug of abuse used either alone or with the serotonergic drug L-(m-trifluoromethylphenyl)piperazine to mimic the neurochemical and behavioral effects of methylenedioxymethamphetamine (Ecstasy) Fantegrossi et al, 2005).…”

Review of the Pharmacology and Clinical Profile of Bupropion, an Antidepressant and Tobacco Use Cessation Agent

“…Operant drug discrimination studies show that bupropion substitutes fully for agents with selective effects on DA systems (e.g., GBR 12909 [1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine]; 111) and fails to substitute for drugs not affecting DA levels or effects, such as selective NET inhibitors (e.g., reboxetine; 37) or â 2 -noradrenergic agonists (e.g., clenbuterol; 102). Moreover, discriminative stimulus effects of bupropion are bidirectional; selective DA agents (e.g., nomifensine; 87,173) substitute for bupropion, whereas non-DA agents do not (e.g., nortriptyline; 11,87,173). Moreover, pretreatment with either DA D 1 or DA D 2 receptor antagonists block the discriminative stimulus effects of bupropion (173), whereas pretreatment with serotonergic or á 1 -noradrenergic receptor antagonists do not (11,174).…”