Nisoxetine and amphetamine share discriminative stimulus properties in mice

Snoddy, Andrew M.; Tessel, Richard E.

doi:10.1016/0091-3057(83)90040-0

Cited by 56 publications

(23 citation statements)

References 24 publications

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“…Together, previous and present data raise the possibility that SERT inhibitors may differently modulate the discriminative stimulus effects of DA indirect agonists in rats and monkeys. Unlike clomipramine, and in agreement with previous studies of NET inhibitors in drug discrimination studies with cocaine or amphetamines (Snoddy and Tessel, 1983;Spealman, 1995;, pretreatment with desipramine and nisoxetine moderately enhanced the discriminative stimulus effects of MA. However, the effects of the two drugs differed qualitatively.…”

supporting

confidence: 71%

Drug Discrimination in Methamphetamine-Trained Monkeys: Effects of Monoamine Transporter Inhibitors

Czoty

Ramanathan²,

Mutschler³

et al. 2004

J Pharmacol Exp Ther

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The involvement of brain monoamine systems in the discriminative stimulus effects of methamphetamine (MA) was studied in squirrel monkeys by evaluating the effects of differentially selective monoamine uptake inhibitors alone and in combination. In monkeys discriminating i.m. injections of 0.3 mg/kg MA from saline, methamphetamine (0.01-0.3 mg/kg), and dopamine transporter (DAT) inhibitors, including 1-{2-(bis(4-fluorophenyl)-methoxy)ethyl}-4-(3-phenylpropyl)piperazine (GBR 12909; 1.0 -17.8 mg/kg) and its analogs AM2502 (1.0 -17.8 mg/kg), AM2506 (1.0 -30.0 mg/kg), AM2515 (1.0 -17.8 mg/kg), and AM2517 (1.0 -5.6 mg/kg), produced dose-related increases in responding on the MA-associated lever and, at the highest doses, full substitution. The time course of MA-like effects was similar for equivalent (3.0 mg/kg) doses of GBR 12909 and its most potent analog, AM2517.Unlike the DAT blockers, the selective 5-hydroxytryptamine (serotonin) uptake inhibitor clomipramine (1.0 -10.0 mg/kg) and the selective norepinepherine (NE) uptake inhibitor desipramine (1.0 -10 mg/kg) produced responding primarily on the saline lever. The selective NE uptake inhibitor nisoxetine partially substituted at the highest dose tested (10.0 mg/kg). Pretreatment with GBR 12909 or AM2517 enhanced the discriminative stimulus effects of MA, shifting the dose-effect curve leftward. The NE uptake inhibitors desipramine or nisoxetine also enhanced the discriminative stimulus effects of MA, whereas clomipramine only attenuated them. These results support the view that dopaminergic mechanisms play a prominent role in the discriminative stimulus effects of MA in monkeys, whereas involvement of serotonergic and noradrenergic systems may be limited to a modulatory role.

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supporting

confidence: 71%

Drug Discrimination in Methamphetamine-Trained Monkeys: Effects of Monoamine Transporter Inhibitors

Czoty

Ramanathan²,

Mutschler³

et al. 2004

J Pharmacol Exp Ther

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“…Abused central stimulant drugs such as the amphetamines, methylphenidate and phenmetrazine produce complete generalization from cocaine (Woolverton 1991), as evidenced again here by the results obtained with d-amphetamine. Previous studies with less efficacious central stimulants have generally provided evidence for amphetamine-like or cocaine-like discriminative stimulus effects as well (Snoddy and Tessel 1983;Kamien and Woolverton 1989;Lamb and Griffiths 1990;Baker et al 1993;Terry et al 1994). In the present study, /-ephedrine also was shown to generalize from cocaine, similar to results obtained earlier in d-amphetamine-and cocaine-trained rats (Huang and Ho 1974;Gauvin et al 1989).…”

Section: Discussionmentioning

confidence: 94%

Evaluation of the cocaine-like discriminative stimulus effects and reinforcing effects of modafinil

1996

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Modafinil [(diphenyl-methyl)sulphinyl-2-acetamide] is a novel psychostimulant drug which is effective in the treatment of narcolepsy and idiopathic hypersomnia. It also has neuroprotective effects in animal models of striatal neuropathology. Although the cellular mechanisms of action of modafinil are poorly understood, it has been shown to have a profile of pharmacological effects that differs considerably from that of amphetamine-like stimulants. There is some evidence that modafinil has central alpha 1-adrenergic agonist effects. In the present study modafinil was evaluated for cocaine-like discriminative stimulus effects in rats and for reinforcing effects in rhesus monkeys maintained on intravenous cocaine self-administration. Modafinil, l-ephedrine and d-amphetamine all produced dose dependent increases in cocaine-lever responding, with maximal levels of 67%, 82% and 100%, respectively. Modafinil produced full substitution in four out of the six rats tested while the highest levels of substitution were associated with substantial response rate decreasing effects. Little evidence was obtained that the discriminative stimulus effects of modafinil were produced by alpha 1-adrenergic activation, based upon results of tests performed in combination with prazosin. In the self-administration procedure, modafinil and l-ephedrine functioned as reinforcers in rhesus monkeys. The reinforcing and discriminative stimulus effects of modafinil-required very high doses: modafinil was over 200 times less potent than d-amphetamine and was also less potent than l-ephedrine. These results show that modafinil has some cocaine-like discriminative stimulus effects and, like other abused stimulants, can serve as a reinforcer at high doses.

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“…Nonetheless, the stimulus properties of a number of drugs have been examined in mice as well. These represent a range of pharmacological classes including stimulants such as cocaine [Middaugh et al, 1998] the amphetamines [Snoddy and Tessel;1983], nicotine [Varvel et al, 1999;Stolerman et al 1999], and pentylenetetrazole [Evans and Balster, 1992], the depressants morphine [Borlongan and Watanabe, 1997], pentobarbital [Balster and Moser, 1987;Rees and Balster, 1988], oxazepam [Rees and Balster, 1988], and ethanol [Rees and Balster, 1988;Grant et al, 1991;Middaugh et al, 1991], non-competitive NMDA antagonists including phencyclidine [Middaugh et al, 1988;English et al, 1999] and dizocilpine [Geter-Douglas and Witkin, 1999] as well as monoamine reuptake inhibitors [fluvoxamine, Gommans et al, 1998;nisoxetine, Snoddy and Tessel;1983] and the atypical antipsychotic agent, clozapine [Philibin et al, 2005]. In the first, and at this time only, report of stimulus control by a hallucinogen in mice, Smith, Barrett, and Sanders-Bush [2003] employed the phenethylamine hallucinogen, 2,5-dimethoxy-4-iodo-amphetamine [DOI; Shulgin and Shulgin, 1991].…”

Section: Introductionmentioning

confidence: 99%

The stimulus properties of LSD in C57BL/6 mice

Winter¹,

Kieres²,

Zimmerman³

et al. 2005

Pharmacology Biochemistry and Behavior

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Rationale-Drug-induced stimulus control has proven to be a powerful tool for the assessment of a wide range of psychoactive drugs. Though a variety of species have been employed, the majority of studies have been in the rat. However, with the development of techniques which permit the genetic modification of mice, the latter species has taken on new importance. Lysergic acid diethylamide [LSD], the prototypic indoleamine hallucinogen, has not previously been trained as a discriminative stimulus in mice.Objective-To demonstrate the feasibility of LSD-induced stimulus control in the mouse and to provide a preliminary characterization of the stimulus properties of LSD in that species.Methods-Male C57BL/6 mice were trained using a left or right nose-poke operant on a fixed-ratio 10, water reinforced task following the injection of lysergic acid diethylamide [LSD, 0.17 or 0.30 mg/kg, SC; 15 min pretreatment] or vehicle.Results-Stimulus control was established in 6 of 16 mice at a dose of LSD of 0.17 mg/kg after 39 sessions. An increase in dose to 0.30 mg/kg for the remaining mice resulted in stimulus control in an additional 5 subjects. In the low dose group, subsequent experiments demonstrated an orderly dose-effect relationship for LSD and a rapid offset of drug action with an absence of LSD effects 60 min after injection. When LSD [0.17 mg/kg] was administered in combination with the selective 5-HT 2A antagonist, M100907, LSD-appropriate responding was significantly but incompletely reduced to approximately 50%; concurrently, response rates declined significantly. In mice trained with a dose of LSD of 0.30 mg/kg, full generalization to the phenethylamine hallucinogen, [-]-2,5-dimethoxy-4-methylamphetamine [DOM] was observed.Conclusions-The present data demonstrate the feasibility of LSD-induced stimulus control in the mouse. The general features of stimulus control by LSD in the mouse closely resemble those observed in the rat but the present data suggest that there may be significant differences as well.

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Nisoxetine and amphetamine share discriminative stimulus properties in mice

Cited by 56 publications

References 24 publications

Drug Discrimination in Methamphetamine-Trained Monkeys: Effects of Monoamine Transporter Inhibitors

Drug Discrimination in Methamphetamine-Trained Monkeys: Effects of Monoamine Transporter Inhibitors

Evaluation of the cocaine-like discriminative stimulus effects and reinforcing effects of modafinil

The stimulus properties of LSD in C57BL/6 mice

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