Dopamine receptors hypersensitivity: further confirmation following drug abuse model.

Controversial multiple investigations have reported that chronic administration of amphetamine or similar drugs in different animals produces a reverse tolerance or a receptor hypersensitivity. However, most studies utilized large doses given chronically and for lengthy periods of time. Real life drug abusers ten to utilize drugs in a cyclic pattern of intermittently increasing doses and then "crashing off" depending on the availability of drugs and psychiatric treatment. In this experiment I intended to demonstrate receptor hypersensitivity with less chronic administration of drugs (in this case only six dosages) given in about two weeks, intermittently, and in increasing dosages to stimulate somewhat closer a drug abuse model. I also utilized a lengthier period of time of waiting in-between the pretreatment and post-treatment evaluation (eight weeks). The subjects were 16 Sprague-Dawley rats of initial weight of 150-200 grams, acclimated to photoelectric cell cages. They were given either D- or L-amphetamine in alternating days for two weeks and in increasing dosages. Both activity and stereotype behavior (SB) were measured. The animals were given eight weeks of rest and then retested with a subthreshold dose of the same drug previously utilized and two days later with the smallest dose of the same medication again. The results showed that the latency and the threshold was decreased and the response was maximized but this was statistically true only for SB, as it did not reach statistical significance for hyperactivity. The relationship of this phenomenon of dopamine receptor hypersensitivity and the clinical findings in dyskinetic disorders, is discussed; also some ideas for further research in this area are brought to light.