Phencyclidine-like catalepsy induced by the excitatory amino acid antagonist DL-2-amino-5-phosphonovalerate

Koek, Wouter; Kleer, Eduardo; Mudar, Pamela; Woods, James H.

doi:10.1016/0166-4328(86)90026-4

Cited by 36 publications

(6 citation statements)

References 7 publications

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“…The results presented in this study support the hypothesis that a reduction of neurotransmission at excitatory synapses utilizing NMDA receptors may underlie certain behavioral effects of PCP (Koek et al, 1986a).…”

Section: Discussionsupporting

confidence: 85%

Excitatory amino acid antagonists induce a phencyclidine-like catalepsy in pigeons: Structure-activity studies☆

et al. 1987

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The excitatory amino acid antagonists D,L-2-amino-5-phosphonovalerate (D,L-AP5), its isomers D-(-)-AP5 and L-(+)-AP5, D,L-2-amino-4-phosphonobutyrate (AP4), D,L-2-amino-7-phosphonoheptanoate (AP7), beta-D-aspartylaminomethylphosphonic acid (ASP-AMP), cis-2,3-piperidinedicarboxylic acid (cis-PDA), and gamma-D-glutamylaminomethylsulphonic acid (GAMS) were tested for their ability to produce a phencyclidine (PCP)-like catalepsy in pigeons when administered intracerebroventricularly. Each of the antagonists produced catalepsy, although L-AP5, and the non-selective antagonists GAMS and cis-PDA, produced the effect only at toxic doses. The rank order of potency to produce catalepsy was AP7 greater than D-AP5 greater than D,L-AP5 greater than cis-PDA greater than ASP-AMP greater than AP4 greater than L-AP5 greater than GAMS; there was a strong positive correlation between this rank order of potency in vivo and the potency order of these compounds in vitro as NMDA antagonists. The antagonists did not displace significant amounts of [3H]N-[1-(2-thienyl)cyclohexyl]piperidine (a congener of phencyclidine) from its recognition site in the brain of pigeon. Thus, the PCP-like catalepsy that is produced by the excitatory neurotransmission at NMDA-preferring receptors that are distinct from, but related to, PCP receptors. The results strongly support the hypothesis that a reduction of neurotransmission at excitatory synapses, utilizing NMDA-preferring receptors, may underlie catalepsy in pigeons induced by PCP.

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Section: Discussionsupporting

confidence: 85%

Excitatory amino acid antagonists induce a phencyclidine-like catalepsy in pigeons: Structure-activity studies☆

et al. 1987

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“…Behavioral studies indicate a unique relationship between NMDA receptors and PCP recognition sites. For instance, animals given the NMDA antagonist 2-amino-5phosphonovalerate behave as if treated with PCP (Koek et al, 1986). Moreover, animals generalize to NMDA antagonists as PCP-like in drug discrimination tests (Willets et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

Anatomic correlation of NMDA and 3H-TCP-labeled receptors in rat brain

1988

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Using quantitative autoradiography, we have compared the regional distribution of N-methyl-D-aspartate (NMDA) receptors labeled with 3H-glutamate and dissociative anesthetic binding sites labeled with 3H-N-(1-[2-thienyl]cyclohexyl)3,4-piperidine (3H-TCP). Binding of both ligands was highest in the hippocampal formation, with high concentrations in a number of cortical and olfactory regions. Intermediate amounts of binding for both ligands were measured in several thalamic and basal telencephalic structures. Very little binding was observed in the hypothalamus, some deep forebrain regions, and most brain-stem structures. Linear-regression analysis comparing the binding at both sites revealed a marked concordance (R = 0.95; p less than 0.001; Pearson product-moment). The granule cell layer of the cerebellum was the only region in which this concordance was not observed. Scatchard analysis of 3H-glutamate binding to NMDA receptors in stratum radiatum of hippocampal formation revealed an apparent single binding site with a Bmax of 9.78 +/- 0.84 pmol/mg protein and KD of 158 +/- 37 nM. 3H-TCP also bound to an apparent single site with a Bmax of 2.07 +/- 0.16 pmol/mg protein and KD of 127 +/- 30 nM. Our results are consistent with the hypothesis that the dissociative anesthetic binding site is linked to the NMDA receptor, and the data suggest that there are approximately 4-5 NMDA binding sites for each dissociative anesthetic binding site.

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“…PCP and pentobarbital increased low probabilities of repetition, without affecting high probabilities, in doses that did not affect the overall rate of responding. Metaphit, a proposed PCP-receptor acylator, and 2-amino-5-phosphonovalerate (AP5), an excitatory amino acid antagonist that induces PCP-like catalepsy in pigeons (Koek et al 1986b), produced effects that were similar to the effects of PCP and pentobarbital, i.e., they increased low probabilities of response repetition, without affecting high probabilities (Koek et al 1986a, c). Conversely, chlordiazepoxide and scopolamine decreased high probabilities of repetition without affecting low probabilities, in doses that also reduced the rate of responding.…”

Section: Discussionmentioning

confidence: 99%

Response repetition in pigeons: pharmacological and behavioral specificity

Koek

Woods

1986

Psychopharmacology

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Using a reinforcement schedule that arranges random sequences of reinforcements over two response keys, low and high probabilities of repetition of non-reinforced responses were generated in two groups of pigeons (n = 3 per group) by varying the probability of reinforcement for responding on the key to which reinforcement was assigned. Unlike rats, the pigeons did not show a tendency to repeat just-reinforced responses, but showed a strong position bias, that was reduced by additional feeding and extinction, but not by any of the drug treatments. Apomorphine increased response repetition, irrespective of the control probability of repetition; d-amphetamine increased low probabilities of repetition, but decreased high probabilities. Chlordiazepoxide and scopolamine selectively decreased high probabilities of repetition; phencyclidine and pentobarbital selectively increased low probabilities of repetition. Morphine, haloperidol, chlorpromazine, additional feeding, and extinction did not affect repetition of non-reinforced responses. Extinction increased perseveration, whereas drug effects on perseveration were not observed. Drug-induced changes of patterning of responses as exemplified herein by drug-induced alterations of repetitiveness may be relevant to the interpretation of drug effects upon performance brought about by other behavioral processes such as discrimination.

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Phencyclidine-like catalepsy induced by the excitatory amino acid antagonist DL-2-amino-5-phosphonovalerate

Cited by 36 publications

References 7 publications

Excitatory amino acid antagonists induce a phencyclidine-like catalepsy in pigeons: Structure-activity studies☆

Excitatory amino acid antagonists induce a phencyclidine-like catalepsy in pigeons: Structure-activity studies☆

Anatomic correlation of NMDA and 3H-TCP-labeled receptors in rat brain

Response repetition in pigeons: pharmacological and behavioral specificity

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