The purpose of this research was to characterize drug-induced rebound cue states using a three-choice, agonist-vehicle-antagonist drug-discrimination procedure. Rats were trained to discriminate among 0.50 mg/kg amphetamine (AM), distilled water (DW), and 0.03 mg/kg haloperidol (HA) in a three-lever drug discrimination task. Time-dependent changes in cue state were assessed following single doses of AM (5 and 10 mg/kg), HA (1 mg/kg), and cocaine (30 and 40 mg/kg). Consistent with expectations derived from the results of a study that used a two-lever AM-HA discrimination task, single doses of AM produced rebound responding on the HA-appropriate lever that was dose-dependent and peaked at 24 h following administration. In addition, cocaine substituted for AM at 0.5-2 h post-injection and then produced HA-like rebound responding that peaked at 24-36 h post-administration. Contrary to expectations, however, rebound AM-like responding did not occur following HA administration. Perhaps two- and three-choice discrimination tasks differ in their ability to characterize qualitative aspects of the post-haloperidol cue state. Knowledge of the time course of drug-induced adaptive processes, measured as withdrawal in the present research, is necessary for a complete description of a drug's effects and is important in understanding the effects of repeated drug administration.

Debate continues as to whether drug discrimination in animals is an inherently quantal or continuous process. This issue is important in determining the appropriate interpretation of results from drug discrimination studies designed to assess the nature of drug-induced interoceptive cues. The quantal approach holds that subjects perceive a drug cue in an all-or-none manner, while the continuous view proposes that when appropriate training and testing procedures are used, subjects can discriminate along a continuum of interoceptive cues. Data consistent with the quantal view have consistently been generated by animals trained to respond on schedules of reinforcement having an FR component. Since quantal responding is a characteristic of these schedules, results from drug discrimination studies using training schedules with FR components are of little value in empirically determining whether drug discrimination reflects a quantal or continuous process. Use of variable schedules of reinforcement might be more appropriate because the pattern of responding generated does not preclude results consistent with either of the competing views. Data from the following studies that trained subjects using VI schedules with a concurrent TO for incorrect lever responding were analyzed: Barrett et al. (1982): L-5-hydroxytryptophan versus saline; Smith (1990): diazepam versus pentylenetetrazol; Barrett et al. (1992): amphetamine versus haloperidol; Barrett and Steranka (1983): amphetamine versus haloperidol. In every case, when experimental conditions produced a group mean intermediate to that for the training drugs, the distribution of scores for individual animals was normally rather than bimodally distributed.

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Serum concentrations of chloramphenicol were determined after oral doses (55 mg/kg body weight) were administered to 7-9 day old Holstein-Friesian calves. Chloramphenicol in an oral solution produced greater serum concentrations than did an equivalent dose of chloramphenicol in capsules (P less than 0.005). A second dose of each formulation administered 12 h after the first dose elevated serum chloramphenicol concentrations significantly (P less than 0.001). The average serum chloramphenicol concentration exceeded 5 micrograms/ml of serum 1 h after administration of the solution compared with 4 h for the capsules. Average serum chloramphenicol concentration was greater than 5 micrograms/ml for at least 12 h after the dose was administered for both formulations. Of the eight calves receiving repeat doses of chloramphenicol, seven (87.5%) developed diarrhea in 76 +/- 8.6 h. Six of the eight calves (75%) died during or shortly after the period of chloramphenicol administration.

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