Effects of methamphetamine on locomotor activity and thalamic gene expression in leptin-deficient obese mice

Abstract

Leptin is an adipose-derived hormone that regulates energy balance. Leptin receptors are expressed in extrahypothalamic sites and several reports showed that leptin can influence feeding and locomotor behavior via direct actions on dopaminergic neurons. The leptin deficient mouse (ob/ob) has been used as an animal model of blunted leptin action, and presents with obesity and mild type 2 diabetes. We used ob/ob mice to study the effect of repeated 7-day methamphetamine (METH) administration analyzing locomotion, behavioral sensitization, and somatosensory thalamic mRNA expression of voltage-gated calcium channels and glutamatergic receptors using RT-PCR. We observed reduced METH-mediated responses in ob/ob mice associated with enhanced in mRNA expression of key voltage-gated and glutamate receptors in the somatosensory thalamus. Results described here are important for understanding the control of locomotion and thalamocortical excitability by leptin.

Different Doses of Methamphetamine Are Needed to Produce Locomotor or Blood Pressure Sensitization in Mice

“…This protocol corresponds to our previous studies and studies by other groups aiming to produce METH sensitization. According to this protocol, results are comparable to those obtained following a longer sensitization period, as used by other groups [ 35 , 36 , 37 , 38 ]. All mice were killed on day 11 immediately after SBP monitoring, which was performed 30 min after the last saline/METH injection.…”

Leptin alters somatosensory thalamic networks by decreasing gaba release from reticular thalamic nucleus and action potential frequency at ventrobasal neurons

“…Thalamic GABA A receptor subunits are regulated developmentally (Gambarana et al 1991; Huntsman and Huguenard 2000; Poulter et al 1992; Zhang et al 1997), and there is a developmental turnover of subunits between postnatal day 6 and 12 in most thalamic nuclei (Laurie et al 1992). Somatosensory thalamic mRNA expression of voltage-gated calcium channels and glutamatergic receptors was altered in adult ob/ob mice compared to their lean WT littermates (González et al 2017). Therefore, altered kinetic properties of IPSCs observed in ob/ob mice could be related to impaired regulation of GABA A receptor subunit expression during neuronal development in the absence of endogenous leptin.…”