IV Nicotine Induced Changes in Hormone Function, Mood States and Behavior

Clinical studies are proposed to analyze the interactions between nicotine, alterations in endocrine hormones, mood and cardiovascular measures. The studies are designed to examine the contribution of gender and menstrual cycle phase. It is hypothesized that analysis of nicotine's rapid hormonal, cardiovascular and subjective effects will be important for developing novel biologic approaches to treatment for nicotine abuse and dependence as well as advancing understanding of the neurobiology of nicotine reinforcement.

These clinical studies are designed to examine the acute effects of intravenous nicotine on anterior pituitary (ACTH, LH) and adrenal hormones (DHEA and cortisol). We also plan to study norepinephrine (NE) and epinephrine (E), because nicotine stimulates rapid release of NE and E in preclinical and clinical studies. The studies will examine the acute effects of intravenous nicotine on the gonadal steroid hormones and the reciprocal feedback regulation by LH. The temporal covariance of hormonal changes with serum nicotine levels and nicotine-induced changes in subjective states and cardiovascular measures will be measured. The covariance between nicotine-induced changes in endocrine, subjective and cardiovascular effects and the temporal concordance with increases in serum nicotine and cotinine levels will be determined. Gender and menstrual cycle phase influences on the effects of nicotine on HPA and HPG hormones and subjective effects will be assessed.

Eligibility Criteria:
Inclusion Criteria:

* Men and women between the ages of 18 and 40 who currently smoke at least 15 cigarettes every day, and who fulfill DSM-IV diagnostic criteria for nicotine dependence (305.10) will be eligible for participation.
* No evidence of clinically significant disease based upon complete medical history and physical examination by Dr. Arthur Siegel (Chief of Internal Medicine, McLean Hospital).
* Absence of DSM-IV Axis I Disorders other than nicotine dependence (305.10) as measured by the Structured Clinical Interview (SCID).
* Routine laboratory blood tests including complete blood count, electrolytes, BUN and creatinine, liver function test, hepatitis panel and urinalysis will be performed. Laboratory parameters must be within the normal range. HBsAg must be negative but subjects who have hepatitis serology consistent with previous exposure to Hepatitis A, Hepatitis B, or Hepatitis C, but who do not have clinical and biochemical evidence of acute infection, will be acceptable.
* Hematocrit levels ≥ 39% for males and ≥ 35% for females.
* Serum pregnancy test (hCG beta subunit) results must be negative within 24 hrs of the study day.
* Normal ECG.
* Subjects must be able to read and understand instructions, as well as provide a valid informed consent.

Exclusion Criteria:

* Women and men with any lifetime DSM-IV Axis I disorder other than nicotine abuse or dependence will be excluded.
* Women who are pregnant will be excluded.
* Women who use hormonal contraceptive medications will not be accepted for participation because this would confound the hormonal measures.
* Men and women with clinically significant medical disorders will be excluded.
* Obese and underweight subjects will be excluded. A mean Body Mass Index (ratio of weight (W) to height (H) squared; W/H2=kg/m2) will be calculated. Women with a mean Body Mass Index (BMI) of between 18.0-27.0 and men with a BMI between 21.4-29.0 will be accepted.
* Treatment seeking subjects will not be selected but will be referred to local smoking cessation programs.