Effects of GABA-B receptor positive modulator on ketamine-induced psychosis-relevant behaviors and hippocampal electrical activity in freely moving rats.
Jingyi Ma, L Stan Leung
Psychopharmacology October 2017 DOI: 10.1007/s00213-017-4705-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study in behaving rats Peer reviewed |
|---|---|
| Population | Long-Evans rats |
| Interventions | CGP7930 Ketamine |
| Dose | CGP7930 1 mg/kg i.p.; CGP7930 0.3 mM/1 µL i.c.v.; CGP7930 5 mg/kg i.p.; ketamine 3 mg/kg subcutaneous |
| Measures | Paired click auditory evoked potentials in the hippocampus (AEP), prepulse inhibition (PPI), locomotor activity, hippocampal gamma (65-100 Hz) waves, paired pulse depression |
| Topics | Ketamine Esketamine |
| Keywords | Cgp7930 Gabab receptor modulator Prepulse inhibition Schizophrenia |
| Key findings | CGP7930 prevented ketamine-induced deficits in prepulse inhibition and hippocampal auditory evoked potential gating, blocked ketamine-induced increases in hippocampal gamma waves, and at a higher dose suppressed ketamine-induced hyperlocomotion, while having no significant effect on these measures when given alone. The authors propose the hippocampus as one neural target of CGP7930 and suggest GABAB receptor modulation may be relevant to schizophrenia. |
Abstract
Decreased GABAB receptor function is proposed to mediate some symptoms of schizophrenia. In this study, we tested the effect of CGP7930, a GABAB receptor positive allosteric modulator, on ketamine-induced psychosis-relevant behaviors and hippocampal electrical activity in behaving rats. Electrodes were bilaterally implanted into the hippocampus, and cannulae were placed into the lateral ventricles of Long-Evans rats. CGP7930 or vehicle was injected intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.), alone or 15 min prior to ketamine (3 mg/kg, subcutaneous) injection. Paired click auditory evoked potentials in the hippocampus (AEP), prepulse inhibition (PPI), and locomotor activity were recorded before and after drug injection. CGP7930 at doses of 1 mg/kg (i.p.) prevented ketamine-induced deficit of PPI. CGP7930 (1 mg/kg i.p.) also prevented the decrease in gating of hippocampal AEP and the increase in hippocampal gamma (65-100 Hz) waves induced by ketamine. Unilateral i.c.v. infusion of CGP7930 (0.3 mM/1 μL) also prevented the decrease in gating of hippocampal AEP induced by ketamine. Ketamine-induced behavioral hyperlocomotion was suppressed by 5 mg/kg i.p. CGP7930. CGP7930 alone, without ketamine, did not significantly affect integrated PPI, locomotion, gating of hippocampal AEP, or gamma waves. CGP7930 (1 mg/kg i.p.) increased heterosynaptically mediated paired pulse depression in the hippocampus, a measure of GABAB receptor function in vivo. CGP7930 reduces the behavioral and electrophysiological disruptions induced by ketamine in animals, and the hippocampus may be one of the neural targets where CGP7930 exerts its actions.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cites 4
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Ketamine activates psychosis and alters limbic blood flow in schizophrenia Neuroreport April 1, 1995
- Ketamine alters oscillatory coupling in the hippocampus Scientific Reports August 2, 2013
- Capturing the angel in "angel dust": twenty years of translational neuroscience studies of NMDA receptor antagonists in animals and humans. Schizophrenia Bulletin September 1, 2012