Abstract
We reported that nicotine applied via a transdermal patch (21 mg/day) induced viral reactivation and ocular shedding in herpes simplex virus type 1 (HSV-1) latent rabbits. One possible mechanism of action involves the release of catecholamines and other similar agents, triggering HSV reactivation. Bupropion (Zyban, Wellbutrin), a non-nicotine aid to smoking cessation, inhibits neuronal uptake of norepinephrine, serotonin, and dopamine. To determine whether bupropion inhibits HSV reactivation, rabbits latent with HSV-1 were grouped (at least 10 rabbits/group) and treated as follows: nicotine patch (transdermal delivery) and bupropion [Zyban sustained-release tablets (150 mg) twice a day (oral)], nicotine patch only, Zyban tablets only [twice a day (oral)], nicotine patch with oral placebo [twice a day (oral)], or no drug treatment. Eyes were swabbed for 22 consecutive days. The appearance of HSV-1 in the tear film was significantly less frequent in the bupropion-treated rabbits, in terms of positive rabbits/total rabbits, positive eyes/total eyes, and positive swabs/total swabs. Nicotine-treated rabbits had 78/440 (17.7%) positive/total swabs, and nicotine/placebo-treated rabbits had 149/792 (18.8%) positive/total swabs, whereas bupropion-treated rabbits had 23/440 (5.2%), and nicotine/bupropion-treated rabbits had 47/792 (5.9%) positive/total swabs. Thus, bupropion significantly reduces nicotine-induced HSV reactivation in latent rabbits.
Footnotes
-
This study was supported by Grants R01EY006311 (to J.M.H.) and P30EY002377 (Louisiana State University Eye Center CORE grant) from the National Eye Institute (National Institutes of Health, Bethesda, MD), by a Senior Scientific Investigator Award (to J.M.H.), by an unrestricted departmental grant (to the Louisiana State University Eye Center) from Research to Prevent Blindness (New York, NY), and by a Dean's Fellowship from the Louisiana State University School of Medicine (to E.R.R.).
-
This work was presented in part at the 28th International Herpesvirus Workshop, July 26 to July 31, 2003 (Madison, WI).
-
doi:10.1124/jpet.104.070862.
-
ABBREVIATIONS: HSV-1, herpes simplex virus type 1; nAChR, nicotinic acetylcholine receptor; ACTH, adrenocorticotropic hormone; LC, liquid chromatography.
- Received May 3, 2004.
- Accepted July 12, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|