Discriminative properties of phencyclidine in mice: generalization to ketamine and monohydroxy metabolites

Middaugh, Lawrence D.; Favara, Jean P.; Boggan, William O.; Stringer, Amy

doi:10.1007/bf00216066

Cited by 8 publications

(7 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At this time, the drug discrimination database (http: \\www.dd-database.org) contains citations for 2532 non-review publications, including 1786 reports of investigations in rats but only 33 studies in mice, none of which involved nicotine. However, good discriminative stimulus control has been found with drugs from a number of classes, including amphetamine in ICR mice (Snoddy and Tessel 1983), pentobarbitone and ethanol in CD-1 mice (Rees et al 1987;Grant et al 1991), phencyclidine in C57BL/ 6 mice (Middaugh et al 1988) and pentylenetetrazol and several volatile anaesthetics in CFW mice (Evans and Balster 1992;Bowen and Balster 1997).…”

Section: Introductionmentioning

confidence: 97%

Discrimination and self-administration of nicotine by inbred strains of mice

Stolerman

Naylor

Elmer³

et al. 1999

Psychopharmacology

View full text Add to dashboard Cite

These studies aim to characterize the discriminative stimulus effects of nicotine in two inbred strains of mice that differ in many pharmacological responses, and to investigate the feasibility of IV self-administration studies with nicotine in one of the strains. For discrimination studies, three groups of C57BL/6 and one group of DBA/2 mice were trained in a two-lever operant conditioning paradigm with a tandem VI-30" FR-10 schedule of food reinforcement. After 40 training sessions, accuracy reached 57.5, 77.5 and 90.0% in C57BL/6 mice trained with (-)-nicotine (SC) in doses of 0.4, 0.8 and 1.6 mg/kg, respectively (n = 8). DBA/2 mice trained with 0.8 mg/kg nicotine attained similar (73.3 %) accuracy (n = 9). Results from extinction tests showed that all groups of mice yielded orderly dose-response curves for nicotine (0.03-1.6 mg/kg), but stimulus control remained notably weaker for the mice trained with 0.4 mg/kg nicotine than for any other group. Overall rates of responding in the undrugged state were lower for DBA/2 than for C57BL/6 mice; DBA/2 mice were also slightly less sensitive than C57BL/6 mice to the response rate-reducing effect of nicotine. The nicotine antagonist mecamylamine (1.5 mg/kg SC) blocked the discriminative stimulus effect of the training dose of nicotine in all groups. The results of the IV self-administration study suggest that nicotine (0.1 mg/kg) can serve as a positive reinforcer in drug-naive C57BL/6J mice (n = 13). Behaviour maintained by 0.1 mg/kg nicotine injections was significantly greater than behaviour maintained by vehicle injections, and it was maintained under an intermittent schedule of reinforcement (FR4). The methods described provide possible approaches for genetic analyses of strain differences in sensitivity to the discriminative and reinforcing stimulus properties of nicotine.

show abstract

Section: Introductionmentioning

confidence: 97%

Discrimination and self-administration of nicotine by inbred strains of mice

Stolerman

Naylor

Elmer³

et al. 1999

Psychopharmacology

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…Mice were tested in six gray Plexiglas two-lever chambers with food pellet dispenser as previously described (Groseclose et al , 1997; Middaugh et al , 1988, 1999, 2000a). Food pellet (20 mg A/I Rodent Pellets, Noyes Co., Lancaster, NH) reinforcers were delivered to a tray located at floor level.…”

Section: Methodsmentioning

confidence: 99%

Effects of vigabatrin, an irreversible GABA transaminase inhibitor, on ethanol reinforcement and ethanol discriminative stimuli in mice

Griffin¹,

Nguyen²,

Deleon³

et al. 2012

Behavioural Pharmacology

View full text Add to dashboard Cite

We tested the hypothesis that the irreversible gamma-amino butyric acid (GABA) transaminase inhibitor, γ-vinyl GABA (Vigabatrin; VGB) would reduce ethanol reinforcement and enhance the discriminative stimulus effect of ethanol, effectively reducing ethanol intake. The present studies used adult C57BL/6J (B6) mice in well-established operant, two-bottle choice consumption, locomotor activity and ethanol discrimination procedures, to examine comprehensively the effects of VGB on ethanol-supported behaviors. VGB dose-dependently reduced operant responding for ethanol as well as ethanol consumption for long periods of time. Importantly, a low dose (200 mg/kg) of VGB was selective for reducing ethanol responding without altering intake of food or water reinforcement. Higher VGB doses (>200 mg/kg) still reduced ethanol intake, but also significantly increased water consumption and, more modestly, increased food consumption. While not affecting locomotor activity on its own, VGB interacted with ethanol to reduce the stimulatory effects of ethanol on locomotion. Finally, VGB (200 mg/kg) significantly enhanced the discriminative stimulus effects of ethanol as evidenced by significant left-ward and up-ward shifts in ethanol generalization curves. Interestingly, VGB treatment was associated with slight increases in blood ethanol concentrations. The reduction in ethanol intake by VGB appears to be related to the ability of VGB to potentiate the pharmacological effects of ethanol.

show abstract

Discriminative properties of phencyclidine in mice: generalization to ketamine and monohydroxy metabolites

Cited by 8 publications

References 6 publications

Discrimination and self-administration of nicotine by inbred strains of mice

Discrimination and self-administration of nicotine by inbred strains of mice

The stimulus properties of LSD in C57BL/6 mice

Effects of vigabatrin, an irreversible GABA transaminase inhibitor, on ethanol reinforcement and ethanol discriminative stimuli in mice

Contact Info

Product

Resources

About