My future research will continue with a major commitment to the study of abuse substances as well as provide a laboratory for the training of both pharmacology and psychology students. The immediate research plan is divided into three sets of interrelated experiments in the rat directed toward furthering our understanding of the neurobehavioral bases of the rewarding effects of abuse substances. The first of these is designed to test further the hypothesis that drug-induced changes in the threshold for rewarding electrical stimulation of the brain of the rat is predictive of abuse liability and that it is an animal model for drug-induced euphoria. The second series of experiments is directed toward the development of a model that allows for the prediction of analgesic efficacy as well as abuse liability of various drugs by means of the effects of these drugs on the threshold for aversive as well as rewarding electrical stimulation of the brain. The third set of experiments is designed to determine if the extent of the effects of abuse substances on the threshold for both rewarding and aversive stimulation is correlated with the specific brain area stimulated. For rewarding stimulation we will compare effects from the medial forebrain bundle (MFB), the periaquaductal grey, and the zona compacta of the substantia nigra. For aversive stimulation we will compare effects from the mesencephalic reticular formation (RF) and the spinal trigeminal nucleus caudalis. In addition, we will determine the effects of single doses and daily administration of morphine on the threshold for brain-stimulation detection (using brain stimulation as a cue) from the MFB and the RF. This procedure allows for the study of drug effects on the perceptual properties of brain stimulation independent of effects on motivational properties. The threshold for three types of electrical stimulation to the brain will be determined in these experiments: brain-stimulation reward, brain-stimulation escape and brain-stimulation detection. The drugs investigated will include opioids, cannabinoids, pentobarbital, combinations of drugs such as d-amphetamine and morphine, tripelennamine and pentazocine, as well as some non abuse substances such as the analgesic, methotrimeprazine.
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