Mesocorticolimbic dopaminergic signaling, which originates in the dopamine (DA) neurons of the ventral tegmental area (VTA) and projects to the nucleus accumbens (NAc) and prefrontal cortex (PFC), governs the control of complex behaviors. Deregulation of mesocorticolimbic dopaminergic signaling has been implicated in a wide range of neuropsychiatric and neurological diseases.
Our laboratory studies the mesocorticolimbic pathway as a mechanism of addiction to drugs like cocaine, nicotine, alcohol, and marijuana. We also investigate dopamine-related disease from the effect on single neurons all the way up to in vivo behavioral experiments. Using electrophysiological techniques, we are exploring concerns about these abnormalities as they pertain to ion channels, synaptic plasticity, and neural circuits.
Function of Type 2 Cannabinoid Receptors in Midbrain Dopamine Neurons
The current prevailing view is that type 1 cannabinoid (CB1) receptors are mainly expressed in neurons of the central nervous system while type 2 cannabinoid receptors (CB2) receptors are predominantly expressed in peripheral immune cells. Our study challenged this view and found that functional CB2 receptors are expressed in VTA DA neurons. Furthermore, these functional CB2 receptors play an important role in cocaine-seeking behaviors in animals.
Additional studies will explore the underlying mechanisms of brain CB2 receotirs, including intrinsic and synaptic modulations, and the role of brain CB2 receptors in drug addiction in the VTA-NAc circuit.
Mechanisms of 5-HT1B Receptors in Midbrain Dopamine Neurons
Serotonin 5-HT1B receptor has been reported to be involved in both stress adaptation and the progression of addiction. The prevailing view suggests that 5-HT1BR activation on medium spiny neurons (MSN) projecting to the VTA decreases GABA release at synapses onto VTA DA neurons, leading to a disinhibition of these neurons, an increase in DA release in the VTA and NAc, and behavioral changes. However, this traditional opinion lacks direct evidence in support. Our study will explore possible new mechanisms of the 5-HT1B receptor in the VTA and its function in vulnerability to stress and drug addiction.