Cocaine hydrochloride

Cocaine hydrochloride was obtained from Mallinckrodt, Inc. (Hazelwood, MO), and was dissolved in sterile saline for injection (U.S.P. grade). Separate stock solutions were prepared for each monkey to insure a similar injection volume across monkeys and the cocaine solution for each monkey was filtered using a 0.22 micron filter (Millipore, Billerica, MA).

Cocaine base was derived from cocaine hydrochloride (Mallinckrodt) by NYSPI pharmacists. Participants were presented with cocaine in an 8 cm glass tube or ‘stem’ fitted with a fine metal screen. Participants held the stem while a nurse held a butane flame on the cocaine until all of it was inhaled. Participants put on eye masks immediately prior to each dosing in order to be blinded to visual cues such as the physical mass of the dose. The placebo condition was inhalation through an empty stem to which a butane flame was similarly applied. After each dose administration, the participant removed the eye mask.

Cocaine base, derived from cocaine hydrochloride (Mallinckrodt Pharmaceuticals, St. Louis, MO), was prepared in pellets of 12, 25 and 50 mg by the New York State Psychiatric Institute (NYSPI) pharmacy (Foltin et al., 1990 (link)). The 0 mg dose consisted of inhaling warm air from the glass stem.
Modafinil (Provigil®) is well absorbed after oral administration and has a terminal elimination half-life of ~12 hrs (Robertson & Hellriegel, 2003 ). Modafinil was packaged by the NYSPI pharmacy into size #00 opaque capsules with lactose filler; matching placebo capsules were filled only with lactose. Because we had previously shown that both 200 and 400 mg/d of modafinil decreased cocaine self-administration (Hart et al., 2008 (link)), 300 mg/d was used in the current study. Under the active medication condition, dosing began with 200 mg on the first day and increased to 300 mg per day for the rest of that phase. Modafinil dose (0, 300 mg/day) order was counter-balanced with 3 of the final 7 participants being tested with modafinil first and 4 being tested with placebo first. Medication (modafinil or placebo) was administered once in the morning (~9:00 AM) and again in the early evening (~5:00 PM). A staff member observed all medication dosing, i.e., a mouth check was performed.

Subjects completed one practice session to familiarize them with experimental measures including the progressive-ratio schedule and drug choice procedure. Four to nine experimental sessions were completed and conducted only on weekdays, at least 24 hours apart. Data from sessions testing 4, 15 and 45 mg intranasal cocaine alone are included here. The remaining sessions either tested a cocaine dose not used in both studies (i.e., 30 mg; Stoops et al., 2010 (link)) or used a bupropion pretreatment condition (Stoops et al., 2012 (link)). Data from those sessions were excluded except as described below. During each session, subjects sampled the cocaine dose available for that day, 4, 15, or 45 mg. They then made six choices between the available dose and a monetary reinforcer (US$0.25) at 30-minute intervals. After making a choice, subjects had to complete a response requirement to earn that choice (see Progressive-Ratio Procedure below). Cocaine doses (4, 15, and 45 mg) were prepared by combining the appropriate amount of cocaine hydrochloride (Mallinckrodt, St. Louis, MO) with lactose to equal a total weight of 60 mg powder and administered in a double-blind fashion.