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W F Caul

Publications and source records attributed to W F Caul.

15 recordsLinked to original sources
PubMed1992

Tolerance, withdrawal, and supersensitivity to dopamine mediated cues in a drug-drug discrimination.

Rats were trained to discriminate between 0.25 mg/kg amphetamine (AMPH) and 0.03 mg/kg haloperidol (HAL) in a two-lever drug discrimination task. In order to test for a drug-induced withdrawal state, animals were assigned to one of three chronic treatment groups and given injections of AMPH, HAL, or distilled water (DW) for 10 consecutive days. Subjects from each treatment condition were then tested at 24, 48, or 72 h after the final injection. At the 24 h retest interval, subjects injected with AMPH responded as though administered an acute dose of HAL (0.028 mg/kg) and subjects injected with chronic HAL responded as though administered an acute dose of AMPH (0.15 mg/kg). By 72 h choice behavior had returned to pretreatment values. To determine whether the rebound observed after 10 days of drug treatment was present after a single injection, independent groups of subjects were injected with single doses of either 10 mg/kg AMPH or 1.0 mg/kg HAL and then retested from 4 h to 48 h later. Single doses of both AMPH and HAL produced significant rebounds that peaked between 20 h (AMPH) and 24 h (HAL) following administration. In a third experiment, animals were tested with or without acute doses of drug following pretreatment with either HAL or AMPH. Receptor supersensitivity accounts for the tolerance observed to HAL 24 h after treatment with 1.0 mg/kg HAL, whereas receptor subsensitivity accounts for the tolerance observed 20 h after treatment with 10 mg/kg AMPH.

Animals↗
PubMed1992

The effects of amphetamine on body weight and energy expenditure.

Although there is evidence suggesting that, in addition to suppressing food consumption, amphetamine reduces body weight by increasing energy expenditure, there is little consistency among the few studies examining that factor. In this experiment, the effect of amphetamine on daily energy consumption, within-day body weights, and hourly measures of metabolic rate (MR) and respiration quotient (RQ) were assessed. Daytime drug injections decreased total energy consumption, produced biphasic changes over time in MR, and persistently lowered RQ values. In contrast, nighttime injections of drug had little effect on energy consumption and MR but did reduce RQ for the first 4 postinjection hours. These effects show that amphetamine effects interact with the circadian organization of behavior and suggest that rodent studies of anorectic agents have more relevance for humans if drugs are given during the night, when rats are normally awake and eating. From this study, it seems clear that amphetamine reduces body weight by altering metabolic rate and fat metabolism in rats when the drug is given during the day.

Animals↗
PubMed1992

Effects of amphetamine on food intake and weight: timing of injections and food access.

Although the effects of amphetamine on food consumption and body weight in nondeprived animals are of interest for theoretical and clinical reasons, there are only a few studies on this topic in the literature. In Experiment 1, independent groups of nondeprived rats were given daily injections of 0, 1, 2, 5, or 10 mg/kg d-amphetamine sulfate shortly after light onset for 30 days. While drug treatment did not affect food consumption, all amphetamine-treated groups lost weight over the initial 12 days and then, over the final 18 days of treatment, gained weight at the same rate as controls. Experiment 2 assessed whether the effects of amphetamine on these measures are influenced by the timing of the daily injections relative to the light-dark cycle. As in Experiment 1, injections of amphetamine at light onset again produced weight loss while not affecting food consumption, whereas injections of the drug at light offset did not reliably affect either measure. Experiment 3 showed that the relationships among variables observed in nondeprived animals remain the same in animals restricted to 12 h of access to food each day and replicated the amphetamine-induced hyperphasia observed earlier by Jones and Caul (9).

Animals↗
PubMed1991

Rebound cue state following a single dose of haloperidol.

It has been reported that chronic administration of haloperidol produces an amphetamine-like rebound cue state. The experiments reported here were designed to assess whether a similar rebound phenomenon would result from a single dose of haloperidol. Rats were trained to discriminate .5 mg/kg amphetamine from distilled water. Five groups were formed to allow testing of haloperidol's effect at 12, 18, 24, 30, and 36 hr postinjection. Each animal was given 0, .5, 1.0, and 1.5 mg/kg haloperidol at its appropriate injection time in a counterbalanced fashion with one week between each test. A shift in the dose-response function of amphetamine that occurred during these weeks, however, precluded appropriate analysis of haloperidol's effects. Given this result, a second experiment was conducted using a between-subjects design. Half of the animals were injected with 1 mg/kg haloperidol 23 hr prior to testing, whereas the others were injected with distilled water. When tested, the haloperidol group responded 33% of the time on the amphetamine-correct lever, whereas the control group responded at 20%. The observation of posthaloperidol rebound in the between-subjects study and the failure to find significant temporal patterns of rebound phenomena using a within-subjects design have both theoretical and methodological importance.

Amphetamine↗
PubMed1989

Drug discrimination training during chronic drug treatment affects the development of tolerance.

The purpose of this experiment was to evaluate the extent to which continued drug discrimination training during chronic drug treatment affects the development of tolerance. Rats were trained to discriminate distilled water from 0.75 mg/kg amphetamine in a two-lever drug discrimination task. Two groups were then given a chronic drug regimen of 13 daily injections of either distilled water or 10 mg/kg amphetamine. Drug discrimination training was continued for half of each chronic drug group. Tolerance was apparent only in the group that was not trained during the chronic amphetamine treatment. The data support the conclusion that continued training throughout the chronic drug treatment provides the opportunity for reinforced correct responding as both nondrug- and drug-cue states are gradually shifted by the chronic drug regimen.

Animals↗
PubMed1989

Time course of the effect of amphetamine on eating is biphasic.

The time course of the effect of 1, 2, and 5 mg/kg d-amphetamine sulfate on eating was recorded in independent groups of rats for 12 days with a measure that was sensitive to both increases and decreases in food consumption. The data from the initial drug treatment day suggest that the time course of the drug's effect was biphasic. Furthermore, during the test period, a clear biphasic temporal response developed to the 2- and 5-mg/kg doses. In both cases, on the last drug treatment day, the drug initially suppressed eating but later produced hyperphagia. The hyperphagic response that developed probably resulted from Pavlovian conditioning of compensatory adaptive responses.

Animals↗
PubMed1988

Amphetamine's effects on food consumption and body weight: the role of adaptive processes.

Three experiments were conducted to characterize the time course of amphetamine's effects on food consumption using procedures that would allow both decreases and increases in eating to be evident relative to control levels. In Experiment 1 we measured eating over 12 postinjection hr in rats. Orderly changes in within-day temporal patterns of eating over the 12 days of amphetamine administration suggest the role of conditioned adaptive processes. In Experiment 2, animals were not presented food until 2 hr after drug administration. Initial anorexia and subsequent hyperphagia were produced by repeated administration of amphetamine. Experiment 3 assessed both within-day and over-day changes in body weight and food consumption and showed that in addition to the drug's anorectic effect, amphetamine also reduces body weight via other mechanisms. In interpreting tolerance to anorectic drugs, it is necessary to evaluate such changes in body weight that indicate shifts in hunger that occur over days as well as shifts in within-day temporal patterns of eating that indicate the presence of conditioned adaptive changes. It is proposed that these two adaptive mechanisms account for pharmacodynamic tolerance.

Animals↗
PubMed1985

Amphetamine-haloperidol discrimination: effects of chronic drug treatment.

Rats responding for food reinforcement were trained in a 2-lever drug discrimination task. Groups of rats were trained to discriminate one of four doses of amphetamine (0.0, 0.1, 0.3, or 0.5 mg/kg) from haloperidol (0.02 mg/kg). Both the rate of acquisition and level of discrimination at asymptote were a function of amphetamine training dose. Following acquisition of this discrimination, choice behavior was assessed in the absence of drug during two test sessions. Twenty-four hours following the second drug-free test session, chronic drug treatment commenced. Half of the animals received 10 mg/kg amphetamine for 10 consecutive days while the other half received 1 mg/kg haloperidol during the same period. Choice behavior was assessed during three 2.5-minute unreinforced drug-free test sessions 24, 48, and 72 hours following the chronic drug regimen. Following chronic haloperidol, animals responded as though a small dose of amphetamine had been administered, while following chronic amphetamine, they responded as though a small dose of haloperidol had been administered. Collectively, these results suggest that animals trained to discriminate amphetamine from haloperidol respond on the basis of a continuum of dopaminergic function. Further, this continuum can be used to elucidate the net effect of pharmacologically-induced alterations in dopaminergic function, as well as the effect of nonpharmacological manipulations that may result in dopaminergic changes.

Amphetamine↗
PubMed1979

Evidence of state dependent learning of brightness discrimination in hypothermic mice.

Shock-elicited escape behavior of C57Bl mice in a brightness discrimination task was examined to investigate the effects of hypothermia on acquisition and reversal. Neither acquisition nor reversal was impaired by 7 degrees C or 13 degrees C decreases in central body temperature when body temperature remained at those levels throughout testing. However, body temperature changes from acquisition to reversal were accompanied by memory deficits during reversal if acquisition occurred at body temperature decreased by 13 degrees and reversal occurred at normal body temperature or body temperature decreased by 7 degrees and reversal at body temperature decreased by 13 degrees. This finding suggests the occurrence of a state dependent discrimination response: an instance of asymmetrical dissociation. In addition, during acquisition, latency of the escape response was longer in hypothermic animals than in controls, and should be interpreted as a performance deficit, rather than failure or delayed rate of learning. Depressed intertrial activity also was observed in hypothermic animals.

Animals↗
PubMed1975

Effects of differential rearing condition on heart rate conditioning and response suppression.

Rats were reared in either an enriched or isolated environment for 60 days following weaning. Neither rearing environment nor sex affected heart rate conditioning. However, when the CS used during conditioning was subsequently presented in a drinking situation, males reared in isolation showed a greater degree of response suppression than did similarly reared females. Males and females reared in the enriched environment did not differ in degree of response suppression.

Acoustic Stimulation↗