2-amino-7-phosphonoheptanoic acid (AP7) produces discriminative stimuli and anticonflict effects similar to diazepam

Bennett, Debra A.; Amrick, Caryl L.

doi:10.1016/0024-3205(86)90488-1

Cited by 109 publications

(26 citation statements)

References 18 publications

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“…In previous studies, baclofen failed to substitute for either chlordiazepoxide in rats (Colpaert et al 1976) or PB in pigeons (Herling et al 1980). In contrast, baclofen produced dose-dependent generalization from diazepam in diazepam-trained rats (Bennett and Amrick 1986). …”

Section: Discussionmentioning

confidence: 91%

Pentobarbital-like discriminative stimulus effects of direct GABA agonists in rats

Grech

Balster

1993

Psychopharmacology

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The discriminative stimulus effects of direct and indirect-acting GABAergic drugs were investigated in rats trained to discriminate 5 mg/kg pentobarbital (PB) from saline under a two-lever fixed ratio (FR) 32 schedule of food reinforcement. PB and diazepam produced dose-dependent substitution for the training dose of PB with response rate reduction only at doses above those producing full substitution. Muscimol, thiomuscimol and 4,5,6,7-tetrahydroisoxazolo [5,4-c]-pyridin-3-ol (THIP) produced intermediate levels of pentobarbital-lever responding (40-60%), accompanied by dose-dependent decreases in rates of responding following THIP and muscimol administration. The GABAA agonist progabide and its metabolite 4-([(4-chlorophenyl) (5-fluoro-2-hydroxyphenyl)methylene]amino)] butyric acid (SL 75102) also partially substituted for PB, producing means of 39-73% PB-lever responding. The GABAB agonist, baclofen, completely failed to substitute for PB even at doses that decreased rates of responding. These results show that the discriminative stimulus effects of indirect GABAA agonists, PB and diazepam, although similar to one another, differ from those of direct GABAA receptor agonists, which produced only partial substitution for PB. The GABAB agonist, baclofen, can be distinguished by lacking any ability to substitute for PB. These results contribute to a further understanding of the similarities and differences in the behavioral effects of different types of GABA agonists.

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Section: Discussionmentioning

confidence: 91%

Pentobarbital-like discriminative stimulus effects of direct GABA agonists in rats

Grech

Balster

1993

Psychopharmacology

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“…Lower doses of MK-801, however, were found in the present study to increase locomotor activity, an effect that is possibly mediated by central catecholamines (Clineschmidt et al 1982b). Competitive (Bennett and Amrick 1986) and non-competitive NMDA antagonists including MK-801 (Clineschmidt et al 1982c) increase anticonflict activity. MK-801 resembles PCP in its discriminative stimulus properties (Tricklebank et al 1987;Willets and Balster 1988), probably due to NMDA antagonism rather than to an agonist action of MK-801 (Tricklebank et al 1987).…”

Section: Discussionmentioning

confidence: 98%

Immediate and long-lasting effects of MK-801 on motor activity, spatial navigation in a swimming pool and EEG in the rat

1989

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In a series of experiments, rats received the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 and measures were made of motor behavior, spatial navigation in a swimming pool, and electroencephalographic (EEG) activity. High doses (0.25-10 mg/kg IV) produced somnolence and akinesia, impaired food consumption, locomotion and swimming, and also impaired navigation to a hidden platform but complete recovery on all measures was obtained between 3 and 5 days postinjection. Lower doses (0.05-0.10 mg/kg, IV) impaired acquisition of a new place response in a swimming pool and produced hyperactivity but did not impair performance on a new cue response or on a well-learned place response. Two forms of hippocampal EEG activity, atropine-sensitive and atropine-resistant EEG were present with the low doses. The results demonstrate that a single dose of MK-801 causes changes in motor behavior and learning lasting a few days, but complete recovery occurs within 5 days of administration of even very high doses of MK-801. They further demonstrate that low doses of the drug selectively impair acquisition of new place responses. Although the general changes in behavior produced by MK-801 suggest that NMDA receptors are involved in many aspects of the control of behavior, the results additionally suggest that NMDA receptors are important for place learning.

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“…1987;Jackson and Sanger 1988;Willetts and Balster 1988b;Willetts et al 1989). Dissociative anesthetics also effect a dose-dependent disruption in rotarod performance, a property shared by other compounds which produce muscle relaxation, sedation and/or ataxia (Zukin and Zukin 1979;Marwaha et al 1981;Bennett and Amrick 1986). However, dissociative anesthetics appear to affect rotarod performance in a manner that is qualitatively different from other substances.…”

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confidence: 80%

A rapid method for evaluating the behavioral effects of phencyclidine-like dissociative anesthetics in mice

1991

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A simple and rapid method for detecting the behavioral effects of phencyclidine and related dissociative anesthetics is described. Dissociative anesthetics such as phencyclidine (PCP) and dizolcipine, which bind with high affinities at N-methyl-D-aspartate (NMDA) coupled cation channels ("PCP receptors"), produced a dose-related increase in the percentage of mice that fell from a 1.5 cm deep circular arena mounted on a 60 cm platform. A similar behavior was not manifest by other classes of compounds examined including competitive NMDA antagonists, an antagonist at strychnine-insensitive glycine receptors, and sigma-receptor ligands with moderate to low affinities for PCP receptors. Pretreatment of mice with glycine reduced in a dose-dependent manner the percentage of falls elicited by a maximally effective dose of dizolcipine. This simple procedure may prove useful for both the rapid detection of dissociative anesthetics and evaluation of putative PCP antagonists.

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2-amino-7-phosphonoheptanoic acid (AP7) produces discriminative stimuli and anticonflict effects similar to diazepam

Cited by 109 publications

References 18 publications

Pentobarbital-like discriminative stimulus effects of direct GABA agonists in rats

Pentobarbital-like discriminative stimulus effects of direct GABA agonists in rats

Immediate and long-lasting effects of MK-801 on motor activity, spatial navigation in a swimming pool and EEG in the rat

A rapid method for evaluating the behavioral effects of phencyclidine-like dissociative anesthetics in mice

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