Effects of the group II metabotropic glutamate receptor agonist, LY354740 on schedule-controlled behaviour in rats

The present study examined the effect of the novel, systemically active Gro up II metabotropic glutamate (mGlu) receptor agonist, LY354740, on schedule -controlled behaviour in rats. Responding for food reward was maintained by three different operant procedures; the first, a three-component conflict schedule; the second, a multiple fixed-interval 60 s/fixed-ratio 10 (FI60/F R10) schedule and the third, a differential reinforcement of low rates of r esponding 10 s (DRL10) schedule, In the first procedure, rats were trained to respond for food on a schedule comprising of variable-interval 30 s (foo d, V130) and fixed-ratio 10 (food + shock, FR10) components separated by ti me-out (TO), LY354740 (1.25-5 mg/kg, i.p.) produced a dose-related reductio n in responding during the VI component and increased responding during the TO component, while having no effect on responding during the punished FR1 0 phase, In the FI60/FR10 schedule, LY354740 produced a dose-related reduct ion in the high rates of responding observed during the FR10 component of t he schedule. Although LY354740 (0.6-10 mg/kg, i.p.) had no effect on the ov erall response rates produced by the F160 component, there was a shift in t he temporal distribution of responding as measured by the quarter-life. LY3 54740 (10 mg/kg, i.p.) increased the low rates towards the start of the int erval, while decreasing the rates of responding towards the end of the FI60 period. In the DRL10 s schedule, LY354740 (5-20 mg/kg, i.p.) had no effect on the total number of responses but produced a significant reduction in t he total number of rewards, suggesting that the temporal control of respond ing had been disrupted, The changes in operant responding occurred at doses that decreased exploratory behaviour, In summary, LY354740 modified respon ding maintained by all three operant schedules at doses which suppressed sp ontaneous activity, These data demonstrate that stimulation of Group II mGl u receptors can produce changes in responding which are dependent on the ba se-line rate of responding, suggesting that mGlu 2/3 receptors may be invol ved in the stimulus and temporal control of behaviour. (C) 1999 Lippincott Williams & Wilkins.