Under physiological conditions, these synapses are capable of expressing a form of potentiation called LTP(GABA), which is modulated by addictive drugs (Nugent et al., 2007). NMDAR activation by a train of high frequency stimulation causes a rise in intracellular calcium, which triggers the release of nitric oxide (NO). NO then acts as a retrograde messenger to activate guanylate cyclase, eventually increasing release from GABAergic terminals. In vivo exposure to morphine prevents LTP(GABA) via interruption of NO to guanylate cyclase signaling (Nugent et al., 2007; Nugent et al., 2009). This inhibition of LTP(GABA) can also be observed following cocaine and nicotine administration, albeit with a distinct time course for each of the drugs tested (Niehaus et al., 2010). Inhibition by morphine can be observed within a couple of hours and lasts approximately 5 days. The effects of nicotine wear off quicker, within 24 hours, while the cocaine-mediated inhibition needs more time to be fully established. Ethanol also blocks LTP(GABA), an effect that is reversed by naloxone, a mu-opioid receptor (MOR) antagonist (Guan and Ye, 2010), suggesting that ethanol may exert its
