Effects of ketamine on monoamine neurotransmittersand GABA in embryonic neurocytes from fetal rat

Abstract

IntroductionKetamine can selectively inhibit specific parts of the central nervous system, especially at the level of the communication channel and the thalamocortical network of the brain. Ketamine is characterized by its peculiar ability to separate pain and consciousness, called "separation anesthesia" (1).Classical ion receptor channels are mainly activated by norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and γ-aminobutyric acid (GABA). These neurotransmitters not only regulate neuronal excitability but also have a strong impact on the development of the brain. For example, DA is retained in vesicles at the nerve endings. When a nerve impulse arrives, the vesicle is emptied and DA is released. DA receptors on the cell membrane can bind to the neurotransmitter, thus transmitting the information. However, neurotransmitters can interact among them. 5-HT antagonist can be enhanced by amphetamine-induced locomotor activity (2) and can inhibit dystonia and catalepsy caused by diazepam (3).However, to this day, little is known about the effects of ketamine on the levels of GABA, DA, NE, 5-HT, and 5-HIAA in neurocyte cell cultures from fetal rats. We thus decided to investigate how different concentrations of ketamine may affect these neurotransmitters at the neurocyte level. Materials and methods AnimalsMale and female Wistar rats, 3 months old and weighing 200 ± 20 g, were purchased from the Animal Experimental Center of the Second Affiliated Hospital of Harbin Medical University (Harbin, China). Prior to the experiment, rats were quarantined for 2 weeks at the Northeast Agricultural University (Harbin, China). A total of 104 rats were randomly divided into low-dose groups (L group, n = 32, 4 subgroups), middle-dose groups (M group, n = 48, 6 subgroups), and high-dose groups (H group, n = 24, 3 subgroups), with 8 rats in each subgroup. Intraperitoneal injections of ketamine (Shenyang Veterinary Drug Factory, 20110908) were as follows: L group with 10, 20, 30, and 40 mg/kg; M group with 50, 60, 70, 80, 90, and 100 mg/kg; and H group with 150, 200, and 300 mg/kg. Cerebrospinal fluid was sampled from the cisterna magna as described previously (4). Cerebrospinal fluid was extracted from the foramen magnum to measure the ketamine concentration