The effects of repeated treatment with 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on the lever press responding of the rat under FI and DRL schedules of food reinforcement.

In general, the effects of 8-OH-DPAT on the body temperature of rats or in inducing the 5-HT syndrome show rapid tolerance. However, in contrast, the 8-OH-DPAT-induced increase in the activity of rats in a two-way active avoidance task only occurs after repeated administration, i.e. there is sensitisation. The present study was conducted to examine whether this developing hyperactivity may also be expressed as increased rates of lever press responding, and if so, under which conditions it occurs. Rats were trained to press levers under fixed interval 60-s (FI 60) or differential reinforcement of low rates 20-s or 72-s (DRL20, DRL72) schedules of food reinforcement. Groups of trained rats were then treated daily 5 min before testing with doses of 0.01, 0.1 and 1.0 mg/kg 8-OH-DPAT SC for 10-21 days. In all three procedures, in the first couple of days of drug treatment, 8-OH-DPAT generally suppressed lever pressing in a dose-dependent manner. Thereafter, tolerance to this effect was seen to a greater (DRL20, DRL72) or lesser (FI60) extent. Some evidence for stimulation of low rates of lever press responding was seen after 10 days treatment under FI60, but not in DRL20 or DRL72 during short 30 to 60 min long daytime tests although in the latter case, the rats responded to the stimulating effects of 0.8 mg/kg SC amphetamine administered once at the end of the experiment. However, when rats were allowed to respond under DRL72 testing for 12 h during the night, after 10 days treatment a clear stimulation of lever pressing was observed. This stimulation was not specific to lever pressing, however, since a stimulation of entries into the food tray and licking were also seen. From these results, it may be concluded that the stimulating effect of 8-OH-DPAT after repeated administration may be expressed as increased rates of lever pressing, but not under all conditions in which psychomotor stimulation by amphetamine is seen. The potential for 8-OH-DPAT and related compounds to stimulate motor responding in this way should be taken into account when interpreting the effects of these drugs in animal models of psychiatric disorders.