One-way generalization of clonidine to the discriminative stimulus produced by cocaine.

Rats were trained to discriminate the stimulus properties of either cocaine or clonidine using a food reinforced two-lever choice paradigm. After training, cocaine was generalized to the cocaine lever in a dose-dependent manner, and clonidine was generalized to the clonidine lever in a dose-dependent manner. Yohimbine, an alpha-2 antagonist, blocked the clonidine stimulus but not the cocaine stimulus. Cocaine was not generalized to the clonidine stimulus; however, clonidine was generalized to the cocaine stimulus, and this generalization was blocked by yohimbine. The one-way generalization of clonidine to cocaine suggests that clonidine has at least two discrete stimulus components: a major component that is not cocaine-like, and a minor component that can be detected by cocaine-trained subjects. In addition, the yohimbine blockade data suggest that both components of the clonidine stimulus are mediated via alpha-2 receptors.