Mitragynine is the major alkaloid found in the leaves of M. speciosa Korth (Rubiaceae), a plant that is native to Southeast Asia. This compound has been used, either traditionally or recreationally, due to its psychostimulant and opioid-like effects. Recently, mitragynine has been shown to exert conditioned place preference (CPP), indicating the rewarding and motivational properties of M. speciosa. Here, the involvement of GABAB receptors in mediating mitragynine reward is studied using a CPP paradigm in rats. First, we examined the effects of GABAB receptor agonist baclofen (1.25, 2.5 and 5 mg/kg) on the acquisition of mitragynine (10 mg/kg)-induced CPP. Second, the involvement of GABAB receptors in the expression of mitragynine-induced CPP was tested. We found that the acquisition of mitragynine-induced CPP could be blocked by higher doses (2.5 and 5 mg/kg) of baclofen. Baclofen at a high dose inhibited locomotor activity and caused a CPP. Furthermore, we found that baclofen (2.5 and 5 mg/kg) also blocked the expression of mitragynine-induced CPP. These findings suggest that both, the acquisition and expression of mitragynine's reinforcing properties is controlled by the GABAB receptor.
Accumulating evidence strongly suggests that gamma amino butyric acid (GABA) receptors play a crucial role in the pathogenesis of Parkinson's disease (PD). Therefore, the present study was designed to investigate the role of GABA-B receptor modulation in experimental models of MPTP-induced PD. MPTP was administered repeatedly on 1st, 7th and 14th day intranigrally for the induction of PD in Male Wistar rats. Baclofen (10 and 20mg/kg) and GABA-B antagonist CGP35348 (10mg/kg) were given after induction of PD for 14 days. Different behavioural tasks were performed during 1st, 14th, 21st, 28th days after MPTP injection and biochemical parameters were estimated on day 28th. Central administration of MPTP showed significant impairment of motor behaviour and marked increase of oxidative damage LPO and GSH in striatum and cortex. Pro-inflammatory cytokines like TNF-α and IL-β were significantly increased in striatum region of MPTP treated rats. However, post treatment with baclofen significantly improved the motor abnormalities and attenuated the oxidative damage and neuro-inflammation in MPTP treated rats. CGP35348, GABA-B receptor antagonist, reversed the protective effect of baclofen GABA-B receptor play role in the neuroprotection. The present study concluded that baclofen produce beneficial effect against MPTP induced PD like symptoms rats through GABAergic mechanism.
The asiatic acid, a triterpenoids isolated from Centella asiatica was used to delineate its inhibitory effect on acetylcholinesterase (AChE) properties, excitatory post synaptic potential (EPSP) and locomotor activity. This study is consistent with asiatic acid having an effect on AChE, a selective GABA(B) receptor agonist and no sedative effect on locomotor.