Dose related acute behavioral and neurochemical profile of pioglitazone.

Diabetics are twice as likely to have depression. It's normal to have long periods of sadness and anxiety. Pioglitazone has important role in the inflammatory response, which suggests that it might have the associated anti-depressant effects being manifested by its anti-depressant profile which needs further exploration. Monitoring changes in behavioral and neurochemical profile of pioglitazone in a dose-dependent manner was the purpose of this study. Pioglitazone was injected to rats at the doses of 0mg/kg, 2.5mg/kg, 5mg/kg and 10mg/kg. Behavioral activities in open field, Skinner's box and elevated plus maze were monitored 20, 35 and 45 minutes respectively after pioglitazone injection. whole brain samples were collected following decapitation of rats one-hour after injection. Samples were kept at -70ºC till HPLC-EC analysis for neurochemical profile. Results show anxiogenic and sedative effects of pioglitazone at all three doses as indicated by Skinner's box, elevated plus maze activity and open field. Also there was an overall decreased dopamine metabolism and increased serotonin turnover. This suggests that diabetic patients using pioglitazone as a therapeutic option, may experience more potent effects of CNS depressants. Findings may help in extending therapeutics in diabetic patients suffering from anxiety and/or depression.

Sonic hedgehog signalling pathway: a complex network.

Sonic Hedgehog (Shh) signalling cascade is one of the intricate signal transduction mechanisms that govern the precisely regulated developmental processes of multicellular organisms. Along with establishing the patterns of cellular differentiation to direct complex organ formation, it also has an important role in post-embryonic tissue regeneration and repair processes. Especially, Shh signalling is implicated in the induction of multifarious neuronal populations in central nervous system. There is compelling evidence of the involvement of Shh protein in the signalling network that regulates various morphogenetic processes such as the exquisite neural tube pattern formation. In the morphogenetic field, the activation of Shh signalling processes is intricately linked to the alterations at the molecular level in the structure of Shh protein that leads to its altered biophysical and biochemical reactivity. This brief article gives an overview of such complex cascade of events in Shh signalling and its transduction pathways.

Regional neurochemical profile following development of apomorphine-induced reinforcement.

Dopamine is primary neurotransmitter which mediates the reinforcing effects of abused drugs, serotonin (5-Hydroxytryptamine; 5-HT) also has a crucial role in the pathophysiology of addiction. The binding sites of various drugs of abuse are different from each other, their final rewarding effects are mediated by an increase in the dopamine level in the Nucleus Accumbens. The present study used conditioned place preference (CPP) test to monitor apomorphine's reinforcing effects. Associated alterations in 5-HT and dopamine metabolism were also monitored in various brain regions by HPLC-EC. Withdrawal from apomorphine administration (at a dose of 1.0 mg/kg on six alternate days) induced reinforcement as monitored in the conditioned place preference (CPP) paradigm. Serotonin and dopamine metabolism was also changed particularly in the ventral and dorsal striatum. Results therefore suggest desensitization of dopamine receptors in the presynaptic site is involved in apomorphine-induced reinforcement. Desensitization of somatodendritic 5-HT(1A) receptors resulting in increased availability of 5-HT at 5-HT(2C) receptors could attenuate apomorphine-induced reinforcement. Therefore, further investigations in this area should focus on attempts to attenuate apomorphine-induced reinforcement by desensitizing somatodendritic 5-HT(1A) receptors.