CONICET | Buscador de Institutos y Recursos Humanos

Leptin is an adipose-derived hormone that acts on hypothalamic leptin receptors to regulate energy balance. Leptin receptors are also expressed in extrahypothalamic sites and several reports showed that leptin can influence feeding and locomotor behavior via direct actions on dopaminergic neurons. Moreover, obesity is often seen an ?eating addiction?. The leptin deficient (ob/ob) is an animal model of obesity and mild type 2 diabetes. Thus, we studied the effect of repeated methamphetamine (METH) administration on adult ob/ob female mice or wild-type. We measured locomotion and RT-PCR mRNA expression (Calcium channels/Glutamatergic receptors) on thalamic Ventrobasal nucleus (VB). Mice were treated with METH (1 mg/kg, sc, 7 days) or vehicle and were sacrificed 4 days after treatment. We found genotype effects: bb/ob showed increased mRNA expression of (1) voltage-gated calcium channels P/Q-type Cacna1a (Cav 2.1), T-type Cav 3.3 (2) hyperpolarization-activated cyclic nucleotide-gated channels Hcn2; and (3) glutamate receptors subunits AMPA-type Gria1 and NMDA-type Grin1. Interestingly, for Hcn2, we have already described a METH effect in mPFC. In this study, ob/ob mice vehicle-injected showed increased Hcn2 in VB while METH-injected ob/ob did not. Also, ob/ob (with signs of leptin deficiency-induced overweight) showed hypo-locomotion and lower velocity in an open field both (after vehicle and METH). Both genotypes showed METH locomotor sensitization (increased locomotion after 7-days compared to day 1) but with lower raw values for ob/ob. Our results suggest that leptin deficiency can alter transcriptional regulation in the thalamus and influence basal and METH elicited-locomotor behavior.PICT 2012-0924, PICT 2012-1769, PICT 2015-2594 and PICT-2014-2499, Argentina/ NIH award P20 GM103425 to UAMS, USA.