Letters to Nature

Nature 393, 76-79 (7 May 1998) | doi:10.1038/30001; Received 30 December 1997; Accepted 26 February 1998

Dramatic decreases in brain reward function during nicotine withdrawal

Mark P. Epping-Jordan2, Shelly S. Watkins1, George F. Koob1 & Athina Markou1

  1. The Scripps Research Institute, Department of Neuropharmacology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
  2. Present address: Glaxo Wellcome Experimental Research S.A., Institut de Biologie Cellulaire et de Morphologie (IBCM), Universit de Lausanne, Rue du Bugnon 9, CH-1005 Lausanne, Switzerland.

Correspondence to: Athina Markou1 Correspondence and requests for materials should be addressed to A.M. (e-mail: Email: amarkou@scripps.edu).

Tobacco smoking is a worldwide public health problem. In the United States alone, over 400,000 deaths and $50 billion in medical costs annually are directly attributed to smoking1. Accumulated evidence indicates that nicotine is the component of tobacco smoke that leads to addiction2, but the means by which nicotine produces addiction remain unclear. Nicotine is less effective as a positive reinforcer than other drugs of abuse in non-dependent animals3. Nevertheless, nicotine-withdrawal symptoms, including depressed mood, anxiety, irritability and craving4,5 in dependent subjects may contribute to the addictive liability of nicotine6,7. We show here that spontaneous nicotine withdrawal in rats resulted in a significant decrease in brain reward function, as measured by elevations in brain reward thresholds, which persisted for four days. Further, systemic injections of a competitive nicotinic-receptor antagonist8 led to a dose-dependent increase in brain reward thresholds in chronic nicotine-treated rats. The decreased function in brain reward systems during nicotine withdrawal is comparable in magnitude and duration to that of other major drugs of abuse9, 10, 11, 12, 13, and may constitute an important motivational factor that contributes to craving, relapse and continued tobacco consumption in humans7.