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Biomedical subjects

K Alling

Publications and source records attributed to K Alling.

11 recordsLinked to original sources

Choice under concurrent VI schedules: comparison of behavior maintained by cocaine or food.

Previous research has shown that concurrent schedule responding maintained by cocaine under short variable-interval (VI) schedules is well described by the generalized matching law. That is, drug-maintained behavior was apportioned in accordance with relative frequency of reinforcement. The purpose of the present experiment was to examine the ability of the generalized matching law to account for choice under longer VI schedules of cocaine availability, and to compare cocaine-maintained to food-maintained behavior in this regard. One group of rhesus monkeys (n = 4) was prepared with indwelling IV catheters and allowed to respond under concurrent VI (conc VI) schedules of cocaine delivery (0.025, 0.05 or 0.1 mg/kg per injection) with an average inter-reinforcer interval (IRI) of 10 or 30 min. In a second group of monkeys (n = 4), a comparable experiment was conducted but with responding maintained by different amounts of food (one, two, or four 1-g banana-flavored pellets). For both groups, the same reinforcer followed responding on either lever, the only difference between the options being the VI schedule, i.e., frequency of reinforcement. The behavior of the cocaine-maintained group was well predicted by the generalized matching law. While both groups evidenced undermatching of both response and time allocation, lever pressing of monkeys whose behavior was maintained by food showed more undermatching than that of the cocaine-maintained group. In addition, a consistent and unexplained bias in responding toward the right lever developed in the food-maintained, but not the cocaine-maintained monkeys. Considering the present results with those of previous experiments, it appears that food-, but not cocaine-maintained behavior, deviates increasingly from strict matching as the IRI is extended. This difference across reinforcers could be due to differences between cocaine and food in the mechanisms by which they maintain behavior, or a direct effect of cocaine on choice performance.

Animals↗

Characterization of unconditioned behavioral effects of dopamine D3/D2 receptor agonists.

A series of experiments examined the ability of dopamine D3/D2 receptor agonists [(+)-(4aR,10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]b enzopyrano-[4,3-b]-1,4-oxazin-9-ol hydrochloride (PD 128,907), (+/-)-7-hydroxy-dipropylaminotetralin hydrobromide (7-OH-DPAT), quinpirole and bromocriptine] to produce a variety of dopaminergically mediated behaviors. The effects of these drugs with selectivity for D3/D2 receptors over D1 receptors were compared with those produced by the selective D1 agonists [(+/-)-Phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride (SKF 38393), (+/-)-6-Chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-be nzazepine hydrobromide (SKF 82958)], a nonselective dopaminergic agonist (apomorphine), and an indirect dopamine agonist (cocaine). The D3/D2 agonists decreased locomotor activity, had no effect on gnawing and only inconsistently induced climbing in mice. Further, these agonists dose-dependently produced scratching in squirrel monkeys. In contrast, the D1 agonists, SKF 82958 and SKF 38393, did not produce scratching in squirrel monkeys. Whereas the full D1 agonist, SKF 82958, produced increases in locomotor activity and in climbing and gnawing, the partial D1 agonist, SKF 38393, did not increase the frequencies of these behaviors. The nonselective dopamine agonist, apomorphine, produced decreases in locomotor activity and increases in climbing and gnawing in mice. Apomorphine dose-dependently produced scratching in squirrel monkeys. The indirect dopamine agonist, cocaine, produced increases in locomotor activity and climbing, but had no effect on climbing or gnawing in mice and did not produce scratching in squirrel monkeys. These findings suggest that D3/D2 agonists can be distinguished on various behavioral measures from the nonselective agonist, apomorphine (gnawing), D1 agonists (scratching) and the indirect agonist, cocaine (locomotor activity and scratching). Behaviors once attributed to stimulation of D2 (locomotor activity and scratching) or D1/D2 (climbing and gnawing) receptors may also involve dopamine D3 receptors.

Animals↗

Assessment of cocaine-like discriminative stimulus effects of dopamine D3 receptor ligands.

The highly selective dopamine D3 receptor ligand, (+)-PD 128907 4aR10bR-(+)-trans-3,4,4a,10b-tetrahydro-4-n-propyl-2H5H[4,3- b]-1,4- oxazin-9-ol), and other dopamine D3 receptor ligands, (+/-)-7-hydroxy-2-(N,N-di-n-propylamino)tetralin and (+)-7-hydroxy-2-(N,N-di-n-propylamino)tetralin, substituted for the discriminative stimulus effects of cocaine in rats, an animal model of subjective effects in humans. Substitution only occurred at doses that markedly decreased responding. These results suggest that dopamine D3 receptors may be involved in the subjective effects of cocaine, and therefore may be a target for the discovery of treatments for cocaine dependence.

Animals↗

The effects of differing response-force requirements on fixed-ratio responding of rats.

Rats were exposed to two-component multiple schedules of food delivery. In the first experiment, 15 responses were required to produce food in both components. A downward force of 0.25 N (25 g) was always required to operate the response lever in one component. In the other, the required force was 0.25, 0.50, 1.00, or 2.00 N (25, 50, 100, or 200 g). In the second experiment, 0.25 N of force operated the lever in one component, but in the other, the force requirement for five consecutive responses at the beginning, middle, or end of each ratio was increased from 0.25 to 2.00 N. In the third experiment, the number of responses required to produce food was reduced from 15 to 5, and then to 1. Again, the effects of altering response force from 0.25 to 2.00 N were examined. In general, as response force increased in all experiments, mean response rates decreased and mean interresponse times increased.

Animals↗

Pharmacological analysis of the scratching produced by dopamine D2 agonists in squirrel monkeys.

Several dopamine agonists, administered i.m., produced persistent, excessive and non-localized scratching in squirrel monkeys (Saimiri sciureus). Studies were conducted with a series of drugs to determine the pharmacological mechanisms responsible for this effect. All of the dopamine D2 agonists studied produced dose-related increases in scratching, whereas several dopamine D1 receptor agonists, indirect dopamine agonists and drugs acting on other receptors failed to produce dose-related increases in scratching. The scratching produced by D2 agonists was stereospecific; (-)-NPA produced scratching whereas its (+)-enantiomer was inactive up to doses 300-fold higher. Scratching induced by quinpirole was attenuated by both D2 and D1 antagonists, and this antagonism was stereospecific, with the D2 antagonist (-)-eticlopride, but not its enantiomer, active. Sensitivity developed to the effects of D2 agonists with the quinpirole dose-effect curve shifting to the left by a factor of approximately 64. Two partial D2 receptor agonists (SDZ 208-911 and SDZ 208-912) had limited efficacy in producing scratching, however, one partial D2 receptor agonist (terguride) was fully efficacious, suggesting that there are spare receptors for this effect. The peripherally active dopamine antagonist domperidone and the histamine antagonist diphenhydramine also reduced the scratching induced by D2 agonists, but not to the same extent as centrally acting D2 antagonists. Scratching in squirrel monkeys is an effect that appears to be due to agonist actions at D2 receptors, and may be mediated by a release of histamine. This behavioral activity may be useful as an in vivo indication of D2 receptor activity in primates.

Animals↗

Effects of cocaine on fixed-ratio responding of rats: modulation by required response force.

The effects of acute cocaine administrations (5.6-32 mg/kg) were determined in rats responding under a multiple fixed-ratio 15 (FR 15) FR 15 schedule of food delivery. The minimum response effort required in one schedule component was 25 g, whereas in the other component it was 200 g. Cocaine produced generally dose-dependent decreases in rate of responding and increases in preratio pause time under each component. There was, however, a significant interaction between force and drug dose, and drug effects were larger in the component requiring 200 g for lever operation. Although a number of other parameters have been shown previously to modulate the effects of cocaine on schedule-controlled responding, the present data constitute the first demonstration that minimum response effort does so.

Animals↗

Self- and cross-citations in the Journal of Applied Behavior Analysis and the Journal of the Experimental Analysis of Behavior: 1983-1992.

We examined self- and cross-citation practices in JABA and JEAB from 1983 through 1992. Mean levels of self-citation for JABA and for JEAB were 22.6% and 36.1%, respectively. Overall, 2.4% of JABA citations were JEAB articles, and 0.6% of JEAB citations were JABA articles, which suggests limited integration of basic and applied research.

Journal Article↗

Effects of d-amphetamine and ethosuximide on responding under delayed-matching-to-sample procedures with differential and nondifferential outcomes.

Pigeons were exposed to delayed-matching-to-sample (DMTS) procedures in which food or a flash of the feeder light followed correct responses. When these consequences were correlated with a particular stimulus (e.g., food followed matching responses to red and a flash of the feeder light followed matching responses to green), accuracy was higher (i.e., stimulus control was greater) than when discriminative stimuli and consequences were not correlated. Although stimulus control in the absence of drug appeared to be weaker under the uncorrelated procedure, neither d-amphetamine (0.5-3.0 mg/kg) in Experiment 1 nor ethosuximide (40-160 mg/kg) in Experiment 2 disrupted accuracy to a greater extent under that procedure. These results, like those of a prior investigation, suggest that drug effects are similar under DMTS procedures regardless of whether correlated or uncorrelated outcomes are arranged.

Animals↗

The effects of phenobarbital on responding under delayed-matching-to-sample procedures with differential and nondifferential outcomes.

Pigeons were exposed to delayed-matching-to-sample procedures in which food or a flash of the feeder light followed correct responses. When these consequences were correlated with a particular stimulus (e.g., food followed matching responses to red and a flash of the feeder light followed matching responses to green), accuracy was significantly higher (i.e., stimulus control was greater) than when discriminative stimuli and consequences were not correlated. Acute administrations of phenobarbital (10-40 mg/kg) produced similar effects regardless of whether or not differential outcomes were arranged for correct responses to a particular stimulus. At doses of 30 and 40 mg/kg, phenobarbital significantly decreased accuracy under both variations of the delayed-matching-to-sample procedure. Given these results, it appears that degree of stimulus control in the absence of drug did not modulate drug effects in the present study.

Animals↗

Free birds aren't fat: Weight gain in captured wild pigeons maintained under laboratory conditions.

Nine feral pigeons, 5 from an urban setting and 4 from a rural setting, were captured and maintained for 42 days under free-feeding conditions comparable to those arranged for laboratory subjects. On average, birds increased their body weights by 17% over this period. The range of increase across birds was 9 to 30%. These findings suggest that the food deprivation arranged for laboratory pigeons, which is characteristically 80% of free-feeding weights, may in some sense be less severe than it first appears.

Journal Article↗

A program for normal glycemic control of insulin-dependent diabetes.

A method of instruction enabling patients to control their diabetes is described. The patients learn through home glucose monitoring how their blood sugar levels vary with changes in diet, exercise, and insulin. They learn to chart accurately all the factors influencing their control in a manner that enables them, as well as the physician, to analyze them quickly. From this information they learn to anticipate the results of various changes in life-style and, thus, to live beyond the customary constraints of the disease without loss of glycemic control. Significant improvements in neuritis, impotence, and creatinine clearance rates are reported.

Adolescent↗