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 Group 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/FR10) schedule and the third, a differential reinforcement of low rates of responding 10 s (DRL10) schedule. In the first procedure, rats were trained to respond for food on a schedule comprising of variable-interval 30 s (food, VI30) and fixed-ratio 10 (food + shock, FR10) components separated by time-out (TO). LY354740 (1.25-5 mg/kg, i.p.) produced a dose-related reduction in responding during the VI component and increased responding during the TO component, while having no effect on responding during the punished FR10 phase. In the FI60/FR10 schedule, LY354740 produced a dose-related reduction in the high rates of responding observed during the FR10 component of the schedule. Although LY354740 (0.6-10 mg/kg, i.p.) had no effect on the overall response rates produced by the FI60 component, there was a shift in the temporal distribution of responding as measured by the quarter-life. LY354740 (10 mg/kg, i.p.) increased the low rates towards the start of the interval, 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 the total number of rewards, suggesting that the temporal control of responding had been disrupted. The changes in operant responding occurred at doses that decreased exploratory behaviour. In summary, LY354740 modified responding maintained by all three operant schedules at doses which suppressed spontaneous activity. These data demonstrate that stimulation of Group II mGlu receptors can produce changes in responding which are dependent on the base-line rate of responding, suggesting that mGlu 2/3 receptors may be involved in the stimulus and temporal control of behaviour.
Moore
N A
NA
Lilly Research Centre, Eli Lilly & Co., Windlesham, Surrey, UK. Moore_Nick_A@Lilly.com
Rees
G
G
Monn
J A
JA
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003220:Conflict, Psychological; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D009042:Motivation; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D012055:Reinforcement Schedule
D014151:Anti-Anxiety Agents; D001643:Bridged Bicyclo Compounds; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C104753:eglumetad