VDCCs and NMDARs underlie two forms of LTP in CA1 hippocampus in vivo.
Animals; Calcium Channel Blockers/*pharmacology; Dizocilpine Maleate/pharmacology; Excitatory Amino Acid Antagonists/*pharmacology; Excitatory Postsynaptic Potentials/drug effects; Hippocampus/*drug effects; Long-Evans; Long-Term Potentiation/*drug effects; Male; Membrane Potentials/physiology; N-Methyl-D-Aspartate/*antagonists & inhibitors; Rats; Receptors; Verapamil/pharmacology
N-methyl-D-aspartate receptor/channel (NMDAR) and voltage-dependent calcium channel (VDCC) antagonists applied independently reduce the magnitude of long-term potentiation (LTP) in area CA1 of the hippocampal slice preparation. When used in combination, the antagonists completely block the induction of LTP. In urethan-anesthetized rats we examined the effect of the NMDAR blocker MK-801 (0.1 mg/kg) and the VDCC blocker Verapamil (10 mg/kg) on LTP induction in area CA1. Extracellular recordings were obtained from stratum radiatum following stimulation of Schaffer collaterals. LTP was induced by a 200-Hz/100-ms tetanus repeated 10 times (2 s isi). Tetanus was given in the presence of intraperitoneal saline, MK-801, Verapamil, or both Verapamil and MK-801. When given separately, Verapamil and MK-801 both significantly reduced the magnitude of LTP as compared with control animals. When given together, the drugs blocked the induction of LTP completely. We conclude that like LTP in vitro, VDCCs and NMDAR underlie two forms of LTP in vivo.
Morgan S L; Teyler T J
Journal of neurophysiology
1999
1999-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jn.1999.82.2.736" target="_blank" rel="noreferrer noopener">10.1152/jn.1999.82.2.736</a>
Acute nicotine and phencyclidine increase locomotor activity of the guinea pig with attenuated potencies relative to their effects on rat or mouse.
Animals; Dizocilpine Maleate/pharmacology; Excitatory Amino Acid Antagonists/pharmacology; Guinea Pigs; Locomotion/*drug effects; Mice; Nicotine/*pharmacology; Phencyclidine/*pharmacology; Rats
Behavioral assays of the responses to psychomotor stimulants can be used to model certain aspects of CNS pathologies such as psychosis and addiction. However, species-dependent differences in the effects of neuromodulators in these assays can confound the interpretation of the results. The goal of this study was to determine the utility of the guinea pig as a model for assessing the behavioral actions of nicotinic receptor agonists and NMDA receptor antagonists. In the present study, the locomotor activity of adult male guinea pigs was measured, prior to and following an acute injection of nicotine, MK-801 or phencyclidine. Each animal received a single dose of the drug. Nicotine produced a dose-dependent increase in activity with an ED(50) of 1.5mg/kg. Phencyclidine also increased activity, with an ED(50) of 3.4 mg/kg. Nicotine produced increases in locomotion in all individual subjects tested, whereas at the maximally-effective dose of phencyclidine, only a fraction of the animals had locomotor activation. There was no change in activity in response to a single dose of MK-801 (0.5mg/kg). Haloperidol had a significant inhibitory effect on locomotor activity independent of the stimulant administered. Thus, both phencyclidine and nicotine are psychomotor stimulants when given to guinea pigs, although the intensity of the response and the potencies of these drugs are lower than in mice or rats under otherwise similar conditions.
Simmons Mark A; Werkheiser Jennifer L; Hudzik Thomas J
Pharmacology, biochemistry, and behavior
2010
2010-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.pbb.2009.10.002" target="_blank" rel="noreferrer noopener">10.1016/j.pbb.2009.10.002</a>
Structure-activity relationships of pentacycloundecylamines at the
Amines/chemical synthesis/chemistry/*pharmacology; Animals; Brain/drug effects; Dizocilpine Maleate/pharmacology; Excitatory Amino Acid Antagonists/*pharmacology; Inbred ICR; Ion Channels; Male; Mice; Models; Molecular; N-Methyl-D-Aspartate/*antagonists & inhibitors; Phencyclidine/analogs & derivatives; Piperidines/pharmacology; Radioligand Assay; Receptors; Structure-Activity Relationship; Synaptosomes/*drug effects; Thiophenes/pharmacology
Prompted by our interest in neuroprotective agents with multiple mechanisms of action, we assessed the structure-activity relationship of a series of pentacycloundecylamine derivatives previously shown to have both L-type calcium channel blocking activity and N-methyl-d-aspartate receptor (NMDAR) antagonistic activity. We utilized a functional assay to measure NMDAR channel block using (45)Ca(2+) influx into synaptoneurosomes. The cage amine
Geldenhuys Werner J; Malan Sarel F; Bloomquist Jeffrey R; Van der Schyf Cornelis J
Bioorganic & medicinal chemistry
2007
2007-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.bmc.2006.09.060" target="_blank" rel="noreferrer noopener">10.1016/j.bmc.2006.09.060</a>