Nicotine Related Brain Activity: The Influence of Smoking History and Blood Nicotine Levels

In this study, we sought to explore brain activity in nicotine-dependent men in response to acute intravenous nicotine using pharmacological magnetic resonance imaging (phMRI).

phMRI was used to evaluate brain activity in response to 1.5 mg/70 kg intravenous nicotine or saline. The nicotine and saline were administered on different visits. The time courses of individual subjects' nicotine levels were used as regressors to assess neural activity relating to the infusions. The influence of Smoking history and physiological measures on the response to nicotine were also investigated.

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 will be eligible for participation.
* No evidence of clinically significant disease based upon complete medical history and physical examination by a qualified physician.
* 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 tests, 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.
* A Body Mass Index (BMI-ratio of weight (W) to height (H) squared; W/H2=kg/m2) of between 18.0 and 27.0 for women and 21.4 to 29 for men.
* Subjects must be able to read and understand instructions, as well as provide a valid informed consent.

Exclusion Criteria:

* Participants with any lifetime DSM-IV Axis I disorder other than nicotine dependence.
* Participants with clinically significant medical disorders.
* Women who are pregnant as determined by laboratory testing for serum beta hCG.
* Women who use hormonal contraceptive medications will not be accepted, because this would confound the hormonal measures.
* Women with a mean BMI of outside the range 18.0-27.0 and men with a BMI outside the range 21.4-29.0.
* Participants with ferromagnetic implants or other contraindications to fMRI

  * Cardiac pacemakers
  * Metal clips on blood vessels (also called stents)
  * Artificial heart valves
  * Artificial arms, hands, legs, etc.
  * Brain stimulator devices
  * Implanted drug pumps
  * Ear implants
  * Eye implants or known metal fragments in eyes
  * Exposure to shrapnel or metal filings (wounded in military combat, sheet metal workers, welders, and others)
  * Other metallic surgical hardware in vital areas
  * Certain tattoos with metallic ink
  * Transdermal patches (eg. Orthro Evra, Nicoderm CQ)
  * Metal IUD (s)
* Participants who describe themselves as seeking treatment will not be selected but will be referred to local smoking cessation programs.