Effects of the preferential dopamine autoreceptor antagonist (+)-AJ76 in the intracranial self-stimulation paradigm

As revealed by locomotor activity experiments in rodents, cis-(1S,2R)-5-methoxy-1-methyl-(2-n-propylamino)tetralin [(+)-AJ76] is a preferential dopamine autoreceptor antagonist that produces stimulatory or weak inhibitory behavioral effects in animals that display low or high baseline activity, respectively. In the present study, the possible positive reinforcing properties of (+)-AJ76 were studied by means of the intracranial (median forebrain bundle) self-stimulation (ICSS) technique in rats. The current intensity of the electrical stimuli was used as the independent variable. The resulting rate/intensity curves were analyzed by computer, and the half-maximal response (called EC50) was calculated for each animal. When starting on a suprathreshold current intensity, (+)-AJ76 dose dependently (3.1-52.0 microM/kg, SC) increased the EC50 without producing any apparent motor deficits like muscular rigidity or catalepsy. A clear-cut and more potent inhibitory action was also noted for haloperidol (0.033-0.133 microM/kg, SC) and the di-N-methyl analog of (+)-AJ76 called (+)-AJ118 (0.8-3.5 microM/kg, SC), while d-amphetamine (1.4 or 5.4 microM/kg, SC) decreased the EC50 values. In the second experiment, animals were subjected to a subthreshold current intensity for 30 min. The intensity was set to produce a response of 15% or less of maximal, shaping response rate for the respective animals. Of these 22 animals, 10 responded with a stimulation, while the ICSS response was inhibited in the others. We did not, however, get consistent results in all rats tested. In summary, this study shows that (+)-AJ76 appears to lack positive reinforcing properties comparable to those produced by classical stimulants such as d-amphetamine.