Phencyclidine-induced stereotypy in rats: Effects of methadone, apomorphine, and naloxone

Verebey, Karl; Kogan, Michael J.; Mulé, S. J.

doi:10.1007/bf00433500

Cited by 28 publications

(8 citation statements)

References 15 publications

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“…These properties are consistent with those of noncompetitive antagonists of the NMDA subclass of glutamate receptors (6)(7)(8), thus suggesting that HU-211 might function as an NMDA-receptor antagonist. This possibility was explored by examining the activity of HU-211 in protecting against the tremorogenic, convulsive, and lethal effects of NMDA in mice.…”

supporting

confidence: 73%

Nonpsychotropic cannabinoid acts as a functional N-methyl-D-aspartate receptor blocker.

Feigenbaum

Bergmann

Richmond

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

168

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Binding studies using the enantiomers of the synthetic cannabinoid 7-hydroxy-A'-tetrahydrocannabinol 1,1-dimethylheptyl homolog in preparations of rat brain cortical membranes reveal that the (+)-(3S,4S) enantiomer HU-211 blocks N-methyl-D-aspartate (NMDA) receptors in a stereospecific manner and that the interaction occurs at binding sites distinct from those of other noncompetitive NMDA antagonists or of glutamate and glycine. Moreover, HU-211 induces stereotypy and locomotor hyperactivity in mice and tachycardia in rat, effects typically caused by NMDA receptor antagonists. HU-211 is also a potent blocker of NMDA-induced tremor, seizures, and lethality in mice. This compound may therefore prove useful as a nonpsychoactive drug that protects against NMDA-receptor-mediated neurotoxicity.The enantiomers of the synthetic cannabinoid 7-hydroxy-A6-tetrahydrocannabinol 1,1-dimethylheptyl homolog have recently been described (1, 2). The (-)-(3R,4R) enantiomer, code-named HU-210 ( Fig. 1), is a highly potent cannabimimetic compound (-80 times more active than &1-tetrahydrocannabinol, the active component of hashish); the (+)-(3S,4S) enantiomer (code-named HU-211) (Fig. 1) is inactive as a cannabimimetic, even at doses several thousand times higher than the ED50 of HU-210 as assayed in a number of tests (2). In characterizing the drug profile of the nonpsychotropic (+) enantiomer HU-211, we noted a striking similarity between its pharmacological, autonomic, and behavioral effects and those of noncompetitive N-methyl-D-aspartate (NMDA) antagonists over a wide range of activities (including stereotypy, locomotor hyperactivity, and tachycardia). This similarity suggested that HU-211 might be functionally active as an NMDA-receptor antagonist. To explore the action of HU-211 and its interaction with specific receptors in the brain, we conducted both pharmacological experiments and binding studies. MATERIALS AND METHODS 3H-labeled N-[1-(2-thienyl)-cyclohexyl]piperidine ([3H]TCP)(40 Ci/mmol; 1 Ci = 37 GBq; >98% pure) was purchased from the Israel Nuclear Center (Negev, Israel). L-Glutamate and glycine were from Sigma; D-(-)-2-amino-5-phosphonovaleric acid (AP-5) and NMDA were from Cambridge Research Biochemicals (Harston, U.K.). HU-211 and HU-210 were synthesized as described (1). Both enantiomers melt at 140-141°C and have identical IR and NMR spectra. administration and tested 60 min after injection. Locomotor hyperactivity was measured as body displacement over 7-cm squares, movement from one square to the next constituting a score of 1. This movement was independently assessed by three trained observers.Heart rate measured over 75 min was determined by the standard transducer-amplifier-recorder technique, and respiratory frequency was visually observed by three trained independent observers with a very high meter-rater correlation. Tremor and seizure were monitored on a platform mounted on four spring-coils. Any vibration of the platform was transduced into an electrical input to an amplifer and then to an osci...

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supporting

confidence: 73%

Nonpsychotropic cannabinoid acts as a functional N-methyl-D-aspartate receptor blocker.

Feigenbaum

Bergmann

Richmond

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

168

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“…DGKβ KO mice also displayed more frequent scratching behavior than WT mice. Stereotypical behaviors such as scratching and head twitching are induced by the administration of psychostimulants [22], and it is also observed in mouse model of psychiatric disorders [23].…”

Section: Discussionmentioning

confidence: 99%

Diacylglycerol Kinase β Knockout Mice Exhibit Lithium-Sensitive Behavioral Abnormalities

et al. 2010

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BackgroundDiacylglycerol kinase (DGK) is an enzyme that phosphorylates diacylglycerol (DG) to produce phosphatidic acid (PA). DGKβ is widely distributed in the central nervous system, such as the olfactory bulb, cerebral cortex, striatum, and hippocampus. Recent studies reported that the splice variant at the COOH-terminal of DGKβ was related to bipolar disorder, but its detailed mechanism is still unknown.Methodology/Principal FindingsIn the present study, we performed behavioral tests using DGKβ knockout (KO) mice to investigate the effects of DGKβ deficits on psychomotor behavior. DGKβ KO mice exhibited some behavioral abnormalities, such as hyperactivity, reduced anxiety, and reduced depression. Additionally, hyperactivity and reduced anxiety were attenuated by the administration of the mood stabilizer, lithium, but not haloperidol, diazepam, or imipramine. Moreover, DGKβ KO mice showed impairment in Akt-glycogen synthesis kinase (GSK) 3β signaling and cortical spine formation.Conclusions/SignificanceThese findings suggest that DGKβ KO mice exhibit lithium-sensitive behavioral abnormalities that are, at least in part, due to the impairment of Akt-GSK3β signaling and cortical spine formation.

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“…However, given the motor stimulant properties of PCP that include locomotor activity and stereotypy (e.g. Murray and Horrita 1979;Verebey et al 1981;Iwamoto 1984;Jacobs et al 2000), the precise effects of systemic PCP on attentional processes is unclear. In some recent studies, however, PCP exacerbated attentional deficits in neonatal hippocampal lesioned animals (Le Pen et al 2003), as well as increase locomotor activity (Hori et al 2000;Kato et al 2000), suggesting a neurodevelopmental pathology of the hippocampus in schizophrenia.…”

Section: Modeling Attentional Dysfunction In Schizophrenia Using the mentioning

confidence: 98%

Psychopharmacological approaches to modulating attention in the five-choice serial reaction time task: implications for schizophrenia

2004

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The monoaminergic and cholinergic systems have independent but complementary roles in attentional function, as measured by the 5CSRTT. These functions are predominantly under the control of the prefrontal cortex and striatum. These conclusions are considered in the context of their application towards therapeutic approaches for attentional disturbances that are typically observed in schizophrenic patients.

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Phencyclidine-induced stereotypy in rats: Effects of methadone, apomorphine, and naloxone

Cited by 28 publications

References 15 publications

Nonpsychotropic cannabinoid acts as a functional N-methyl-D-aspartate receptor blocker.

Nonpsychotropic cannabinoid acts as a functional N-methyl-D-aspartate receptor blocker.

Diacylglycerol Kinase β Knockout Mice Exhibit Lithium-Sensitive Behavioral Abnormalities

Psychopharmacological approaches to modulating attention in the five-choice serial reaction time task: implications for schizophrenia

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