We have recently proposed a quantitative pharmacological model of maintained cocaine self-administration that states that the intervals (T) between self-administrations are described by the equation:

T = ln(1 + D_U/D_ST) * t_1/2 /0.693

where D_U is the cocaine unit dose, D_ST is the minimum maintained level of cocaine (the satiety threshold) and t_1/2 is the cocaine elimination half-life [1]. In Sprague-Dawley rats the satiety threshold was calculated to be approximately 2.0 mg/kg. Moreover, a direct method for the measurement of cocaine priming threshold determined was developed. It was determined that the reinstatement of cocaine self-administration requires the level of cocaine to be at or above that produced by an i.v. injection of 0.2 mg [2]). Therefore, the cocaine level in the body appears fundamental in the regulation of responding for cocaine.

We have developed a software package that permits:

1. Flexibility in the self-administration sessions. Sessions are typically divided into five distinct stages: 1) extinction of cue-induced presses, 2) reinstatement, 3) loading, 4) maintenance and 5) extinction of cocaine-induced presses.
2. Present drugs or food and signals according to any desirable schedule: fixed, proportional, variable or progressive.
3. Calculate the cumulative levels of cocaine at any time during a self-administration session. Particular emphasis is placed on the reporting of the calculated levels of cocaine at the time of each cocaine injection.
4. Record the absolute time of every event (events are: any lever presses, pumps or signals activation and deactivation, etc.).
5. Export the data to a database.
6. Present the cumulative record of drug administration events and the corresponding cocaine levels graphically immediately after the session.
7. Calculate the priming threshold, the satiety threshold, the intervals at any unit doses of cocaine used in the experiment etc.

Using this software package we have demonstrated that the cocaine levels rise rapidly following reinstatement, corresponding to the drug-loading phase of a session. Approximately 5-15 min after reinstatement, the inter-injection intervals abruptly become longer, but remain regular. During this maintenance phase of a session the calculated cocaine levels at the initiation of each injection are observed to remain constant at all unit doses. Extinction responding is related to the declining cocaine levels.

Hardware and software requirements are:

• Operant chambers and interfaces from Med-Associates, Georgia, VT, U.S.A.
• Med-PC software for Windows from Med-Associates.
• IBM compatible PC with Windows 95 or 98.
• Database (for example InterBase or Microsoft Access).
• Sigma Plot or similar graphics program.

References

1. Brain Research, 839, 85-93 (1999).
2. Brain Research, 831, 165-174 (1999).

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