Effect of Methamphetamine Exposure on Expression of Calcium Binding Proteins in Rat Frontal Cortex and Hippocampus

Abstract

Methamphetamine (METH) is a psychostimulant drug with potent effects on the central nervous system that can cause psychotic symptoms similar to those of schizophrenia. Specific alterations in GABAergic neuronal markers have been reported in schizophrenia and animal models of psychotic illness. The aim of this study was to determine whether there are changes in subpopulations of GABAergic neurons, defined by the presence of calcium binding proteins (CBPs), in animal models of METH abuse. Rats received acute (Binge) doses of 4 × 6 mg/kg, a chronic escalating dose regime (0.1-4 mg/kg over 14 days) or a combination of the two and were compared with a vehicle-administered control group. Brains were taken and sections of frontal cortex (Cg1) and hippocampus (dentate gyrus and CA1-3 regions) underwent immunostaining for three CBPs [parvalbumin (PV), calbindin (CB), and calretinin (CR)]. Significant decreases in PV-immunoreactive (IR) neurons in each METH group and all regions were observed. Smaller METH-induced deficits in CB-IR cells were observed, reaching significance primarily following chronic METH regimes, while CR-IR was significantly reduced only in frontal cortex following chronic administration. These results suggest that METH regimes in rats can induce selective deficits in GABAergic neuronal subtypes similar to those seen in schizophrenia and may underlie the psychosis and/or cognitive impairment that can occur in METH abuse and dependence.

<p>Effect of pre- and post-treatment with<em> Bacopa</em> <em>monnieri</em> (Brahmi) on phencyclidine-induced disruptions in object recognition memory and cerebral calbindin, parvalbumin, and calretinin immunoreactivity in rats</p>

“…While diminishing numbers of CB and PV were found throughout the prefrontal cortex, striatum, and CA1–3, the selective depletion of CR found in the prefrontal cortex suggested that the vulnerability of this CBP was probably more prominent in that region. This finding was consistent with the previous study using a Methamphetamine-induced schizophrenic-like model which reported that cortical CR immunoreactivity was more vulnerable than those in hippocampal regions 42. It was suggested that GABAergic neurons expressing CR were not changed in schizophrenia 45.…”

“…It was found that the schizophrenic-like model in the neuroprotective effect study and in the cognitive enhancement effect study had decreases in CB and PV immunoreactivity neurons in the prefrontal cortex, striatum, and CA1–3. Deficits of both CB and PV immunoreactivity were previously reported in the frontal cortex from the schizophrenic-like model 40–42. Deficits in PV immunoreactivity were also investigated in the hippocampus of both schizophrenic-like models and patients 42–44.…”

“…Deficits of both CB and PV immunoreactivity were previously reported in the frontal cortex from the schizophrenic-like model 40–42. Deficits in PV immunoreactivity were also investigated in the hippocampus of both schizophrenic-like models and patients 42–44. However, the study in the striatum has not been reported previously.…”

Increased DNA Methylation in the Parvalbumin Gene Promoter is Associated with Methamphetamine Dependence

“…In the longer term the drug can have neurotoxic effects on several neurotransmitter systems, including that of GABA [4,5]. This has recent support both from pharmacogenetic studies of association between METH psychosis and polymorphisms in the GABA synthetic enzyme glutamate decarboxylase (GAD) genes [6] and from findings, in an animal model of METH abuse, of deficits in, most strongly, the parvalbumin (PV)containing subtype of GABergic neurons in frontal cortex and hippocampus [7].…”

Modelling the cognitive and neuropathological features of schizophrenia with phencyclidine

“…Nevertheless, in support of the key role of PV deficits in modelling schizophrenia, we and others have demonstrated this pathology in a range of other rodent models, developmental and pharmacological, that can produce behavioural deficits modelling certain aspects of schizophrenia. These include isolation rearing (Harte et al, 2007), prenatal or neonatal inflammatory challenge with lipopolysaccharide (Jenkins et al, 2009; Wischhof et al, 2015) and chronic or acute high-dose methamphetamine (Veerasakul et al, 2016). Others have observed PV neuronal losses following prenatal methylazoxymethanol (Penschuck et al, 2006) or repeated ketamine administration (Sabbagh et al, 2013).…”