Rats were trained to use the right forelimb to exert continuous downward pressure on a force transducer and simultaneously to drink sweetened milk from a dipper controlled by the emitted force. Oscillations in forelimb force during this performance were spectrally analyzed to describe the tremorogenic effects of haloperidol (0.04, 0.08, or 0.16 mg/kg). Haloperidol reduced time-on-task and increased the variance of force oscillations in the 10.0-25.0-Hz frequency band. When atropine sulfate (5 mg/kg) was given along with haloperidol, time-on-task was partially restored, and the effects of haloperidol on the 10.0-25.0-Hz band were diminished. These data suggest that the behavioral deficits produced by relatively low doses of haloperidol in rats are analogous (and possibly homologous) to neuroleptic-induced Parkinsonian symptoms in humans.
The reinforcing effect of the high affinity dopamine reuptake inhibitor GBR 12909 (1-[2-[bis(4-fluorophenyl)methoxy]ethyl)-4(3- phenylpropyl)piperazine) was compared with that of cocaine, and the effects of both GBR 12909 and cocaine pretreatments were evaluated on behaviour maintained by cocaine in rhesus monkeys. Increasing dose per injection of intravenously-delivered GBR 12909 or cocaine led to increased rates of lever-press responding. Maximum cocaine-maintained rates were higher and occurred at a smaller dose than maximum rates of GBR 12909-maintained responding. Presession intravenous administration of either GBR 12909 or cocaine (0.32, 1.0 or 3.2 mg/kg) resulted in dose-dependent decreases in rates of cocaine-maintained responding when high doses of cocaine, which engendered high response rates, were available early in the session. Under these conditions, the decrease in response rates was associated primarily with decreases in running rate rather than with a lengthening in post-reinforcement pause times. The decreases in running rate produced by both cocaine and GBR 12909 probably reflect an unconditioned rate-disruptive effect of these drugs on cocaine-reinforced responding rather than a reduction in the reinforcing efficacy of cocaine.
Behavior maintained by intravenously delivered alfentanil, cocaine, or ketamine was assessed using a fixed-ratio schedule of reinforcement. As the dose of each drug was increased, rate of responding also increased up to a maximum. Further increases in dose resulted in decreased response rates (inverted U-shaped curve). An analysis of postreinforcement-pause-time and run-time measures for the ascending limb of the inverted U-shaped functions revealed that behavior was characterized by systematic decreases in both pause time and run time as dose and rate increased. An examination of the descending limb of the dose-response functions revealed that lowered response rates for cocaine and ketamine were correlated with increases in run time and small and inconsistent effects on postreinforcement pause time. Behavior maintained by rate-reducing doses of alfentanil was characterized by lengthened postreinforcement pauses with small increases in run time. These data suggest that at larger doses, drug reinforcers may have unconditioned or direct effects on the behavior that the drug is maintaining, and more important, that the nature of these unconditioned effects depends on the drug that is maintaining behavior.
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