Pharmacology and Toxicology

Research Interest:

Research in my laboratory focuses on understanding the mechanism of cocaine addiction. Drugs of abuse such as cocaine and nicotine stimulate the reward circuit of the brain to produce pleasure. A key component of the reward circuit is the mesolimbic dopamine system that consists of dopamine projections from the ventral tegmental area (VTA) in the midbrain to nucleus accumbens (NAc), prefrontal cortex (PFC) and other forebrain regions. Following repeated drug administration, adaptive cellular and molecular changes occur in these areas and translate into behavioral changes, producing intense drug craving and compulsive drug seeking.

A useful strategy for understanding the mechanism of drug addiction is to identify drug-induced changes in the brain, as some of these changes must be responsible for the development of addictive behaviors.  A primary target of drugs of abuse is the synapse. We make patch clamp electrophysiological recording and optical imaging from rat and mouse brain slices to study how drugs of abuse affect synaptic transmission and plasticity in the reward circuit. The slice preparation is accessible to a variety of physiological and pharmacological manipulations and permits us to identify drug-induced alternations in synaptic plasticity and to dissect their underlying mechanisms in same experiments.

Following the identification of drug-induced changes in the reward circuit, we will determine if these changes are directly responsible for the formation of addictive behaviors. Toward this end, we will investigate whether enhancing and blocking the identified change affect drug-induced addictive behaviors. Locomotor sensitization, conditioned place preference and drug self-administration are useful animal models for assessing addictive behaviors. These studies may uncover new targets for therapeutic intervention in drug addiction.

Recent Publications

Pan B, Hillard CJ, Liu QS (2008) Endocannabinoid signaling mediates cocaine-induced inhibitory synaptic plasticity in midbrain dopamine neurons. J Neurosci 28:1385-1397.

Pu L, Liu Q S, Poo MM: BDNF-dependent synaptic sensitization in midbrain dopamine neurons after cocaine withdrawal.  Nat Neurosci. 2006 May;9(5):605-7. Epub 2006 Apr 23. 

Liu QS, Pu L, Poo MM: Repeated cocaine exposure in vivo facilitates LTP induction in midbrain dopamine neurons. Nature. 2005 Oct 13;437(7061):1027-31.