RAT INTRAVENOUS SELF-ADMINISTRATION

Animals

Studies are conducted in adult male and female Sprague Dawley rats (Envigo) in an AAALAC-accredited facility with approval from an Institutional Animal Care and Use Committee, and implemented in accordance with the Guide for the Care and Use of Laboratory Animals 8th Edition (National Research Council, 2011) with standards set by the National Institutes of Health.

Experimental procedure

Self-administration studies are used to evaluate the potential for abuse liability of assets. Most drugs that are abused in humans are self-administered by laboratory animals, and most drugs that are not self-administered by laboratory animals are not abused in humans.

The self-administration procedure is conducted using appropriate group sizes determined by power analysis. Male and female rats (n=10-15) are evaluated in separate cohorts. Dose-responses are investigated, and vehicle and positive control groups are included to establish the validity of the experiment. For all animals, experimenters are blinded to the treatments.

Intravenous self-administration takes place in sound attenuated operant chambers (Med Associates, VT) equipped with two levers: the active lever delivers the asset, and the other lever is inactive. The self-administration procedure includes several steps adapted from Chang et al., 2015.

• Food training: rats are food-restricted and trained for about a week to press on the active lever to obtain food. Rats are included in the study if they reach a predetermined threshold.
• Acquisition training: rats are allowed to self-administer compound solutions by pressing the active lever in a fixed-ratio schedule of reinforcement during one hour daily until stable self-administration is achieved (typically 20 days for commonly abused compounds in several categories).
• Progressive ratio schedule: after acquisition training, the break point is assessed using a progressive ratio schedule of reinforcement in which the number of responses required to obtain the drug infusion progressively increases. The session is terminated at the end of the 1-hour or after a 20 min period without active lever presses.

This work was conducted by PsychoGenics Inc. (Paramus, NJ) in collaboration with PSPP, NINDS, NIH under contract # 75N95019D00026