their night cycle. Probes implanted in control animals were perfused throughout the night with a standard perfusion medium (Ringer), whereas experimental subjects had the perfusion solution switched to one containing the indirect cholinergic agonist neostigmine after 3 hr. Results showed a dramatic (and nearly complete) cessation of feeding during neostigmine exposure. Lack of eating was apparently not due to incapacitation or immobility, since water intake was unaffected in these animals (data not shown). Conversely, a situation in which ACh is depleted can cause hyperphagia (Fig. 3). For these experiments, rats were trained to lever-press for access to 45 mg food pellets during a 10 min interval each day for several weeks. After a stable baseline of responding was established, one half of the subjects received bilateral NAc injections of ethylcholine azirdinium mustard (AF64A), a compound which has relatively selective toxic effects on ACh neurons, while control animals received vehicle injections. Again, results were profound but in the opposite direction as observed before. In this case, AF64A-treated animals exhibited a 2-fold increase in responding for food. Activity on a food-inactive lever was unaffected (data not shown) indicating that the increase in bar pressing was not simply a consequence of hyperactivity.
