PubMed Health⌕ Search

Biomedical subjects

P M Duncan

Publications and source records attributed to P M Duncan.

At least 19 recordsLinked to original sources

Conditioned compensatory response to ethanol as indicated by locomotor activity in rats.

Spontaneous motor activity (SMA) was used to investigate conditioned tolerance to the depressant effect of ethanol, and conditioned responses to stimuli predicting ethanol injection. Rats were injected with saline or ethanol at 800 or 1600 mg/kg, on alternate days, in two distinctly different locations, over a period of 20 conditioning days. The two ethanol doses were administered to separate groups of rats, but conditioned effects were determined by within-subject comparisons. Conditioned SMA responses (rearing and ambulatory activity) were measured after injection of saline in the location previously paired with ethanol treatment, and conditioned tolerance was determined by observing ethanol effects in rats tested in the environment previously paired with saline treatment. Ethanol-paired stimuli increased SMA (both activity measures, both dose-groups) during the conditioned response test. Absence of these conditioned stimuli during the tolerance test resulted in greater behavioral depression with the 800 mg/kg ethanol dose for both the rearing and ambulation measures; however, this effect was seen with the 1600 mg/kg dose for the rearing measure only. These results provide further evidence that Pavlovian conditioning is involved in tolerance to the depressant action of ethanol on overt behavior, and demonstrate the presence of such conditioned compensatory responses in the absence of ethanol treatment.

Animals↗

Effect of combinations of insulin, glucose and scopolamine on radial arm maze performance.

Previous research has shown that glucose is an effective agent in facilitating memory performance and in attenuating scopolamine-induced amnesia. Although insulin has not been shown to facilitate unimpaired memory, a previous study has demonstrated that insulin can also attenuate scopolamine-degraded memory. The present study was designed to determine how different combinations of insulin, glucose and scopolamine affect memory. It involved nine rats whose memory was assessed through performance in a win-shift radial arm maze task under different drug treatments. A 2 x 2 x 2 (insulin x glucose x scopolamine) within-subjects design with a 5-h drug test interval was employed. Scopolamine disrupted memory performance, and both glucose and insulin counteracted this disruption. Combining the glucose and insulin treatments did not increase their ability to attenuate scopolamine deficits but slightly decreased this effect. Glucose tended to enhance memory, even in the absence of scopolamine, whereas insulin had no effect on memory in the absence of scopolamine. Blood glucose levels were measured and did not indicate changes caused by drug treatments. The memory effects may have been due to the acetylcholine-agonist actions of glucose and insulin, an interpretation consistent with previous research findings.

Animals↗

The role of sympathetic arousal in discrimination of insulin-produced hypoglycemia.

Hypoglycemia, as produced by insulin administration, elicits counter-regulatory processes including sympathetic nervous system arousal. Humans report that these autonomic responses are salient cues in the recognition of hypoglycemia. The role of these autonomic responses in the recognition of the hypoglycemic state by rats was investigated in this experiment. Nine rats were trained to discriminate the normal state of euglycemia from the hypoglycemia produced by the injection of 2 units/kg insulin, which caused a reduction in blood glucose levels to 66-77% of baseline values. A 'drug discrimination' procedure was used with a food-motivated operant. After extensive training, reliable hypoglycemia discrimination was established, in that the mean percentage of total test-period responses on the 'hypoglycemia' lever was 78% after insulin treatment, compared to 16% after water injection. Tests were then conducted after the injection of epinephrine (and no insulin), and after the injection of insulin plus propranolol, with the intention of eliciting sympathetic activity during euglycemia, and blocking sympathetic responses during hypoglycemia. These manipulations failed to simulate or to block the hypoglycemia cue, with the insulin or non-insulin operant response choice being essentially unchanged. These results indicate that in rats beta-adrenergic sympathetic responses are not critical for the recognition of hypoglycemia. Appropriate discriminative responses were apparently made on the basis of the impairment by hypoglycemia of central nervous system (CNS) function ('neuroglycopenic' effects), although a role for cholinergic activity of the sympathetic nervous system cannot be ruled out.

Adrenergic Agonists↗

Discrimination of insulin-produced hypoglycemia in rats.

Hypoglycemia is an abnormal state that can be induced by administering insulin to a fasting animal. Rats were trained to discriminate the normal state of euglycemia from the hypoglycemia produced by injection of 6 units/kg insulin. A drug discrimination procedure was used with a two-lever operant response. Insulin or water injected 25 min prior to the operant sessions determined whether left or right lever presses were reinforced. During 40 training sessions, reliable discrimination of the insulin-produced cue developed. After insulin injection, mean blood glucose levels dropped to about 75% of preinjection values. At 12 min postinsulin injection, prior to the development of hypoglycemia, noninsulin responses were made. Noninsulin responses were also made after injection with 800 mg/kg ethanol, indicating that a novel interoceptive state did not substitute for the insulin-produced cue. Insulin injections produced less severe hypoglycemia in less food-deprived rats, which again gave noninsulin responses. Animals can be trained to recognize the insulin-produced state, which presumably involves hypoglycemia, and/or counterregulatory process evoked in response to the drop in blood glucose.

Animals↗

The effect of training dose on discrimination of compound drug-exteroceptive stimuli.

Rats were trained to discriminate between two compound stimulus arrays that included exteroceptive (ES) and interoceptive (IS) stimulus components. The ES components were illumination and tactile cues, and the IS components were produced by d-amphetamine (A) or Na pentobarbital (P) treatment (drug versus drug discrimination). The relative ES-IS strength was then determined by testing with "mismatched" stimulus arrays consisting of combinations of ES and IS components that had not been presented simultaneously during training. Additional tests were done with ES only (no drug treatments). At training doses of 0.8 mg/kg A versus 10 mg/kg P, the ES were less salient than, but did share stimulus control with, the stronger IS components. In a second group, trained with lower doses (0.5 mg/kg A versus 4 mg/kg P), the ES were much more salient than the IS, although again, both types of stimuli did acquire some control. This dose-related sharing of stimulus control between ES and IS components is similar to relationships among components of compound arrays consisting entirely of ES, and thus further illustrates similarity between drug-produced and exteroceptive stimuli.

Animals↗

Growth and intellectual development.

Data from the National Health Examination Survey (cycles II and III) provided a representative sample of 13,887 US youths (6 to 17 years of age) with which to examine the relationship between height (normalized for age and sex) and measures of intellectual development (Wechsler Intelligence Scale for Children) and academic achievement (Wide Range Achievement Test). Additionally, 2,177 subjects were studied first in cycle II and 2 to 5 years later in cycle III, forming a well-selected longitudinal study group in which to examine any association between linear growth and change in IQ scores. Wechsler Intelligence Scale for Children and Wide Range Achievement Test scores were significantly correlated with height in both cycle II and cycle III. However, no significant association between change in relative height and change in IQ scores could be detected in the longitudinal group. These data suggest that therapies designed to increase height are unlikely to alter measures of intellectual development or academic achievement.

Achievement↗

Phencyclidine raises kindled seizure thresholds.

Phencyclidine (PCP) has been reported to have both anesthetic and seizure-inducing properties. In the present experiment the effect of PCP on previously established seizures, kindled in the amygdala, was examined, using rats as subjects. In a repeated measures design three doses of PCP (1, 2 and 5 mg/kg) were compared with a saline control condition. The high dose of PCP was found to significantly increase seizural afterdischarge thresholds, while not affecting seizure durations.

Amygdala↗

Ethanol-amphetamine interaction effects on spontaneous motor activity and fixed-interval responding.

The spontaneous motor activity (SMA) of rats was recorded after injections of saline, d-amphetamine sulfate (0.8 mg/kg), and ethanol (400, 800, 1200, and 1600 mg/kg). Each drug treatment was given separately, and the amphetamine treatment was also combined with each ethanol dose. Ethanol, when injected without amphetamine, produced a dose-related decrement in SMA. Amphetamine, injected without ethanol, produced an increase in SMA. The combination of ethanol at 400 mg/kg with amphetamine potentiated the amphetamine-stimulant effect, but higher doses of ethanol counteracted amphetamine-produced increment in SMA. In a second experiment, similar combinations of ethanol and amphetamine were administered to rats lever-pressing for food pellets under a fixed-interval reinforcement schedule. The effect of amphetamine alone depended on baseline rate and varied among individual rats. Ethanol had a depressant effect on response rates, but combinations of the two drug treatments produced rates that, in most rats, were higher than after any single drug or saline treatment.

Animals↗

The effect of ethanol on wheel running in rats.

Rats were given IP injections of ethanol at 0, 400, 800 and 1200 mg/kg. Their activity in running wheels was recorded for one hour post-injection. Ethanol at 800 and 1200 mg/kg depressed running. This effect was greatest during the first 15 min post-injection when activity levels were highest in the nondrugged condition. No evidence of an ethanol-produced increase in running was seen. The monotonic, dose-related activity decrement with no biphasic effect from ethanol in wheel running is similar to some reports of this drug's effect on rats in other paradigms, such as food-motivated operant responding and spontaneous motor activity.

Animals↗

Interaction between discrimination of drug states and external stimuli.

Rats learned a two-choice operant response by discriminating differences between external stimuli, internal (drug-produced) stimuli, or a combination of these two types of stimuli. Separate groups of rats were used for each stimulus condition. A tactile and visual external cue was superior to the ethanol-saline cue in producing stimulus control, but the group receiving both drug and external stimulus cues performed in a manner very similar to the external cue-only group. The two stimulus sources thus did not "add" to promote more rapid or complete discrimination. After acquisition of discrimination, previously coincident drug and external stimulus states were reversed to determine which stimulus source had more behavioral control. This test for stimulus selectivity indicated that the external stimulus had essentially complete control of response choice.

Animals↗

The effect of external stimulus change on ethanol-produced dissociation.

Rats which were subjected to aversive Pavlovian conditioning while in a state of ethanol-produced intoxication showed significantly less conditioned suppression of water drinking in the non-drugged state only if the external stimulus situation was also changed between conditioning and testing. This interaction between internal and external stimulus change supports a generalization-decrement explanation of drug-produced dissociation of memory. The number of conditioning trials was also manipulated, but this variable had no significant effect on the conditioned responses. In a second experiment, ethanol injections were given again shortly before testing. This treatment caused a normal degree of conditioned drinking suppression in rats conditioned in the ethanol state, indicating that state-dependent learning was responsible for the conditioned response deficit seen in the first experiment. The dissociation was asymmetrical since rats injected with ethanol before testing only showed a high degree of conditioned suppression.

Animals↗

Asymmetrical state dependency from temporary septal area dysfunction in rats.

Rats with cannulas implanted in the septal area were conditioned, tested, or both conditioned and tested shortly after intracerebral injection of local anesthetic via the cannulas. A 2 X 2 factorial design was used to determine whether the presumed state of temporary septal area dysfunction, previously shown to produce amnesia, has state-dependent properties. A state-dependent learning effect was observed in the rats both conditioned and tested in the dysfunctional stat remembered the aversive conditioning better than those conditioned in the dysfunctional state but tested in the normal state. Since rats conditioned in the normal state but tested during septal dysfunction did appear to exhibit conditioned fear when tested, the state-dependent effect was asymmetrical. Performance effects of the procaine injection were observed and accounted for in determining the state-dependent nature of temporary septal area dysfunction.

Animals↗