Jordan Spencer and Dr. Scott C. Steffensen PhD, Department of Psychology and Center for Neuroscience

Introduction:

Alcohol abuse is prevalent in today’s society, causing an economic burden to the US of several hundred billions of dollars annually in direct costs alone. Several reports have estimated that 80% of those with a dependence on alcohol are also smokers. While smoking rates in the general population have decreased in recent decades, the use of NIC has remained high (approximately 70-75%) in individuals who regularly use alcohol. Often taken in concert, the use of tobacco and alcohol are leading causes of preventable death in the United States. In addition, there is strong evidence of co-dependence – individuals who smoke are ten times more likely to be alcoholics.

This being the case the proposed experiment has the intention of gathering information regarding the mechanism underlying the co-dependence of nicotine (NIC) and alcohol through exploration of the role of α6 nicotinic acetylcholine receptors (nAChRs) on ethanol effects on dopamine (DA) release in the pleasure system of the brain.

Methodology:

Anesthetized (Isoflurane) rats underwent terminal brain surgery, where holes were drilled in the skull allowing room for both stimulating and recording electrodes. These electrodes allow us to measure dopamine release and reuptake using Fast Scan Cyclic Voltammetry (FSCV). After creating a baseline DA release of a given neuron the rodent was given an administration of one of many combinations of the following substances via intravenous injection: Ethanol, nicotine, and specific antagonist and agonist of alpha/beta subunits. The experimental results were then gathered and recorded using demon voltammetry software.

Ex-vivo experiment were also conducted which involved harvesting brain slices, and then placing them in an ex-vivo microscope rig. These give us the ability to target the specific area of the brain that we wish to study, in this case the Nucleus Accumbens. The substances mentioned above are simply added to the ACSF which is being used to cycle over the slice to preserve it.

Results:

The pharmacology of nicotine inhibition of DA release in the shell resulted in the a6*-nAChR antagonist a-CtxMII had no effect on nicotine inhibition of DA release at 0.1 mM, the a4b2 antagonist DHbE significantly reduced nicotine inhibition of DA release in the NAc.

Whereas in the core we found that the a6*-nAChR both antagonists a-conotoxins a-CtxMII and a-CtxMII significantly reduced nicotine inhibition of DA release in the NAc core.

These results demonstrate different pharmacological results in both of these regions of the brain.

Ethanol showed similar results regarding ethanol inhibition of DA release in the core. While the a7-nAChR antagonist MLA did not alter ethanol inhibition of DA release, the a6*-nAChR antagonist a-CtxMII significantly reduced ethanol inhibition of DA release in the NAc core.

Conclusion:

The reduced inhibition of DA release by both nicotine and ethanol when a6 nAChR antagonists are present demonstrates to some degree similar mechanistic functions in regards to the NAc core. This was not the case however in the NAc shell. This similar mechanism while not a definitive proof sheds further light on the co-dependence of Nic and EtOH.