Reproductive and behavioral control in the male and female cat with progestins: long-term field observations in individual animals.
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Tolerance to the effects of cocaine on key pecking by pigeons, maintained by differently valued fixed-interval schedules of food presentation, was studied. Key pecking was established on a multiple fixed-interval 5-sec fixed-interval 30-sec fixed-interval 120-sec schedule. Cocaine (1.0-10.0 mg/kg) was administered acutely and then chronically (i.e., before each session) in 5.6 mg/kg doses. Acute cocaine administration produced dose-related decreases in response rates under all three schedules. When cocaine was administered chronically, response rates either recovered fully, or increased to the extent that no reinforcers were missed during the sessions. The development of tolerance was not systematically related to the schedule value. Considered in relation to previous research, these results indicate that different control rates of reinforcement, within the schedules and parameters studied, do not contribute to tolerance to cocaine's behavioral effects.
Female Sprague-Dawley rats were trained to lever press for food on a variable interval one minute schedule of reinforcement. Four of these rats were then made tolerant to and physically dependent on morphine by a series of automatic IV injections. Four other rats were made tolerant to and physically dependent on LAAM. During the dependence state behavioral tolerance was exhibited to the suppressant effect of morphine on lever pressing, but not to the suppressant effect of LAAM. Abstinence was induced by discontinuation of injections. During both the morphine and LAAM abstinence states from the fourth through twelfth days mean lever presses per session were significantly higher than pre-drug control values. However, there were quantitative differences. Mean lever presses per session were significantly higher during morphine abstinence than during LAAM abstinence. This difference in degree of increased lever pressing observed during morphine and LAAM abstinence in this study extends our previous reports which demonstrated that in the rat morphine abstinence was associated with more severe behavioral disruptions than LAAM abstinence.
The role of the serotoninergic and opioid systems in the choice between a passive defensive and an orienting response of the mollusc Lymnaea stagnalis to the presentation of an unfamiliar object was studied. Under the influence of 5-HTP, a metabolic precursor of serotonin, orienting and investigatory behavior was activated; the number of protective reactions decreased. Under the influence of naloxone, an antagonist of opiate receptors, the proportion of orienting responses decreased, and the number of passive defensive avoidance and freezing reactions increased. The influence of the agents investigated on the attitude of the snail to a novel object was found to be well coordinated with their influence on other forms of behavior and the behavioral state of the mollusc as a whole.
RATIONALE: Opioid receptors are divided into three types: kappa, mu, and delta receptors. Receptor-selective antagonists are useful experimental tools for evaluation of opioid receptor-mediated processes. 5'-Guanidinonaltrindole (GNTI) was recently developed as a novel kappa-selective antagonist. OBJECTIVES: To evaluate the potency, time course, and selectivity of GNTI's opioid antagonist effects in rhesus monkeys in an assay of schedule-controlled responding. METHODS: Five rhesus monkeys were trained to respond under a fixed ratio 30 schedule of food reinforcement. The rate-decreasing effects of the kappa agonists U50,488 and U69,593, the mu agonist morphine, and the delta agonist SNC80 were examined alone and after pretreatment with GNTI (0.1 and 1.0 mg/kg i.m.; 1 h to 14 days). RESULTS: U50,488, U69,593, morphine, and SNC80 dose-dependently decreased response rates in this procedure. GNTI produced a dose- and time-dependent antagonism of the rate-decreasing effects of U50,488. The kappa antagonist effects of GNTI had a slow onset and a long duration of action, and peak antagonist effects were observed after 24 h. A higher dose of 3.2 mg/kg GNTI eliminated responding in one monkey and was not studied further. The antagonist effects of GNTI were kappa selective, because 1.0 mg/kg GNTI also antagonized the effects of U69,593, but not those of morphine or SNC80. CONCLUSIONS: These results suggest that GNTI is a potent and selective kappa antagonist with a slow onset and long duration of action in rhesus monkeys. Relative to the prototype kappa antagonist nor-binaltorphimine, GNTI may have some advantages as a tool for the study of kappa receptor-mediated processes.
A paradigm for the control of visual fixation of the macaque monkey in vision experiments was described. Using a Maxwellian view, the procedure permits the placement of discrete test-light stimuli in a specific area of the retina as the monkey fixates a primary target. This procedure holds foveal fixation as other behaviorally significant visual stimuli are presented to the visual field. By a methods-of-limits procedure, the sensitivity of the monkey eye was measured at different retinal locations under both photopic and scotopic visual adaptation.
The effects of acute and chronic administration of phencyclidine (PCP) were examined in five male squirrel monkeys trained to respond on a chain fixed-interval fixed-ratio schedule of food presentation. Acute PCP (0.01-0.60) mg/kg i.m.) produced dose-related decreases in response rate during both components of the schedule. Both components were equally affected by the drug. The effects of the drug on fixed-interval response rate were dependent on the control rate of responding in corresponding segments of the interval. After the initial dose-response determination, the subjects were placed on an individualized regimen of chronic PCP administration lasting from 82 to 126 days, beginning with daily injections for 2 days alternating with saline injections for 2 days, progressing to four injections daily. No evidence of physical dependence was seen upon withdrawal of the drug. Redetermination of the dose-response function for PCP (0.03-1.0 mg/kg i.m.) demonstrated a nearly 2-fold shift to the right of both the fixed-interval and fixed-ratio dose-response curves, indicating tolerance. In addition, the subjects' behavior recovered sooner from a dose of PCP (0.60 mg/kg i.m.) given after the chronic regimen than from the same dose given before the chronic regimen. The results demonstrate that tolerance can occur to the behavioral effects of PCP in the squirrel monkey.
Pigeons were trained under a multiple schedule of food presentation with alternating 30-response fixed-ratio (FR-30) and 10-minute fixed-interval (FI-10) components. Average rates of responding were 2.9 and 0.55 responses/sec, respectively. Both phencyclidine (0.03-3.0 mg/kg i.m.) and ketamine (0.1-30.0 mg/kg i.m.) increased response rates at low doses while decreasing response rates at high doses during the FI-10 component. Only a dose-related decrease in response rates was seen in the FR-30 component with both phencyclidine and ketamine. In individual birds, the maximum rate increases in the FI-10 component ranged from 110% to 163% of the control rate. The rate increases in the FI-10 component depended on the control rate of responding. The effects of phencyclidine and ketamine were qualitatively similar to d-amphetamine (0.1-10 mg/kg i.m.).
Right coronary blood flow (CBF) was measured in 11 mongrel dogs during classical aversive conditioning (a 30 s tone followed by a 1 s 2-6 mA electrical shock). The cardiovascular response consisted of significant (P less than 0.01) increases in: mean arterial pressure (12.9%), systolic right ventricular pressure (RVP, 31.8%), d(RVP)/dt (49.9%) and heart rate (56.2%). The coronary vascular response to behavioral stress consisted of an immediate and significant increase in mean CBF (56.9%) coupled with a significant decrease in mean coronary vascular resistance (CVR, -28.5%). The mean CVR decrease was reduced by cardioselective beta-blockade (CBB) or cardiac pacing and eliminated by right stellectomy (RSGx). The combination of CBB with cardiac pacing resulted in a significant increase in mean CVR. alpha-adrenergic blockade with either phentolamine or prazosin, RSGx, and cardiac pacing significantly reduced the control mean CVR values. Thus, these data suggest that the right coronary response to stress is primarily mediated by the release of metabolic factors secondarily to an increased inotropic or chronotropic state. However, when these metabolic effects were controlled, mean coronary resistance no longer decreased but, rather, increased in response to the aversive stress. This increase could be eliminated by the addition of an alpha-adrenergic antagonist. These data further suggest that the coronary response to behavioral stress activates an alpha-adrenergic vasoconstriction.
Within the scope of a cross-section study the Fear of Death Questionnaire (Hensle 1977), the Semantic Differential of the term Death (Potthoff 1980) and the IPC questionnaire (Krampen 1981) were submitted to n = 186 first- and second-year medical students and to n = 151 third- and fourth-year medical students. This was to trace the question how far the attitude toward death and the locus of control of medical students vary in the course of their education. In comparison with most of other respective publications our paper did not show any significant changes of their attitude toward death and their locuis of control neither. After more detailed analysis of the data discerning consideration of the fear of death questionnaire mentioned above is to be demanded prior to further use in medical fields. At least in view of medical students it's value regarding the construct validity is to be questioned. Concerning the Semantic Differential at least one adjective pair should be eliminated in future.
The response of mice of breaking a light beam onto a photocell was programmed to produce food according to a multiple schedule with alternating 30-response fixed ratio, 300-second fixed interval (FR-30 FI-300 sec) components. Training was standardized for all mice, and stable patterns of responding that were similar to those described for other species and responses under this schedule developed quickly. The effects of pentobaribtal, delta-amphetamine, phencyclidine and ketamine were studied. At some dose, each of the four drugs produced an increase in rate of responding; the increase was proportionately greater at low rates of responding than at higher rates. At some dose range, delta-amphetamine, ketamine and phencyclidine produced dose-related increases in FI average rates were to 1.83, 1.25 and 1.32 times the control rate for delta-amphetamine (1 mg/kg), ketamine (100 mg/kg) and phencyclidine (3 mg/kg), respectively. Phencyclidine and ketamine thus showed some "amphetamine-like" effects in the mouse. Pentobarbital increased (1.25 times the control rate) both the FR and FI response rates at a dose of 3 mg/kg. Higher doses of pentobarbital progressively decreased both FR and FI response rates in a parallel fashion.
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Previous reports have suggested that the effects of the benzodiazepine antagonist flumazenil diminish over repeated exposure in subjects treated chronically with a benzodiazepine agonist. The current study examined whether the frequency of exposure to flumazenil altered its potency in decreasing rates of responding in monkeys treated with chlordiazepoxide (CDP). Three monkeys responded under a multiple fixed ratio (FR10:FR10) schedule of food presentation and stimulus-shock termination (SST). In untreated monkeys, flumazenil (0.1-3.2 mg/kg) had no effect in either component. After 2 weeks of treatment with 32.0 mg/kg per day of CDP, flumazenil decreased response rates in the food component, with a dose of 3.2 mg/kg decreasing rates to 10% of control; rates in the SST component were not altered by flumazenil. When flumazenil dose-effect curves were redetermined at 28-, 14-, 7-, 4-, 2- or 1-day intervals, there was no further change in the potency of flumazenil in decreasing food-maintained responding. When CDP treatment was terminated, the potency of flumazenil recovered to pre-CDP values within 23 days. These results suggest that dependence develops to CDP, since changes in the potency of flumazenil co-varied with CDP treatment. Moreover, it does not appear as though results from previous reports, that showed a diminished response to frequently-administered flumazenil, can be generalized to all conditions.
Effects of cocaine on several behaviors considered to be reflective of psychomotor stimulation were compared in F344/CR1BR and NBR/NIH inbred rat strains. Effects of cocaine on locomotor activity were compared with effects on either bar-press or nose-poke responses maintained under a multiple fixed-interval 3-min, timeout 1-min schedule of food presentation. In locomotor activity experiments, NBR rats were twice as active as F344 rats under baseline conditions and displayed dose-dependent increases in locomotion (5-20 mg/kg). Maximal increases in locomotor activity of F344 rats were only 200% compared to 1000% in NBR rats. In contrast to locomotor activity, no strain differences in the effects of cocaine were observed under the schedules of food delivery. Bar-pressing under the fixed-interval schedule was increased to a maximum of 150% of control in both rat strains. Nose-poke responding under the fixed-interval schedule was not significantly increased, but timeout rates were increased in both strains. These results suggest that NBR and F344 rats do not differ in general sensitivity to stimulant effects of cocaine but exhibit marked differences in responsivity to cocaine that are dependent upon the behavior studied. Further delineation of the behavioral specificity of strain differences in sensitivity to cocaine should help to identify neurobiological substrates underlying unique biologically determined responses to cocaine.
The present experiments were designed to study the influence of prediction and control of electric shocks on various aspects of immune function, and the possible intermediate role of glucocorticoid hormones. After two sessions of inescapable footshocks, the reactivity of splenocytes to concanavalin A was reduced by one third. This effect was completely reversed when each shock was preceded by a warning stimulus, even though the adrenocortical response was the same in both conditions. In another experiment, rats were submitted to ten sessions of continuous avoidance in a shuttle-box and a group of yoked animals received the same footshocks without any relationship to their shuttling behavior. Although yoked rats displayed a reduced reactivity of splenocytes to lectins, animals of the avoidance group had a reduced antibody response to sheep erythrocytes. In contrast, no difference was observed in the corticosterone or prolactin response. These data further support the importance of psychological factors on stress-induced changes in immune functions. Furthermore, they demonstrate that various aspects of the immune system are differentially affected by behavioral factors and the results argue against a major role for the adrenocortical system in mediating these changes.
To examine the effects of repeated administration of corticotropin-releasing factor (CRF) on behavior, rats were administered ICV injections of either CRF or saline on alternate days for 10 days prior to performing on a multiple fixed-interval (FI) 60 s/fixed-ratio (FR) 20 schedule for food reinforcement. A daily session consisted of 10 components of each schedule that alternated, starting with the FI component. CRF doses were individually determined for each rat and were either 1.0, 3.0, or 10 micrograms CRF based upon the dose that occasioned more than a 50% reduction in the rate of responding. Acute administration of CRF decreased the rate of responding in both components well below control rates; this decrease in responding was associated with a 20 or 50% decrease in the number of earned reinforcements in the FI and FR components, respectively. With repeated administration, CRF-induced suppression of responding was attenuated, although CRF continued to decrease response rate. Despite the continued reduction in response rate, subsequent CRF injections did not result in a loss of reinforcements in the FI component, whereas rats continued to lose 20% of the reinforcers in the FR component. After an 18-day hiatus in which no CRF was administered, the baseline rate of responding on the multiple schedule increased, in particular in the FI component. When CRF was readministered, response rates were slightly suppressed relative to a reestablished saline control but significantly higher than CRF-induced suppression on the last day of the chronic regimen. These data demonstrate that with repeated administration tolerance develops to CRF-induced suppression of responding in rats.
Lever pressing by squirrel monkeys was maintained by i.v. injections of nicotine (3-560 microgram/kg) or cocaine (3-300 microgram/kg) under two intermittent schedules of self-administration. Under a fixed-interval schedule, the first response after a specified interval of time produced an injection. Under a second-order fixed-interval schedule, the completion of every 10-response fixed-ratio unit produced a brief visual stimulus and the first fixed-ratio unit completed after a specified interval produced both the brief stimulus and an injection. As the dose of either drug was increased, the rate of responding first increased and then decreased; maximal response rates maintained by nicotine were approximately equal to those maintained by cocaine in some monkeys, but less than those maintained by cocaine in other monkeys. Patterns of responding maintained by the two drugs were qualitatively similar in all monkeys and were characteristic of performances maintained by other reinforcers under fixed-interval or second-order fixed-interval schedules. Doses of nicotine greater than 30 microgram/kg/injection usually produced vomiting, but often maintained responding well above the rates maintained by saline. When the nicotinic antagonist, mecamylamine (1.0 mg/kg i.m.) was administered before every experimental session, responding maintained by nicotine, but not by cocaine, fell to within saline-control levels; increasing the dose of nicotine to as high as 1700 microgram/kg/injection did not restore responding. Under the intermittent schedules studied here, nicotine served as an effective reinforcer to maintain responding and the reinforcing effects of nicotine were blocked by mecamylamine.