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PubMed2002

Differential cortical acetylcholine release in rats performing a sustained attention task versus behavioral control tasks that do not explicitly tax attention.

The present study used microdialysis techniques to compare acetylcholine release in the frontoparietal cortex of rats performing in a task requiring sustained attention with that of rats performing in two control procedures. The two control procedures were a fixed-interval 9-s schedule of reinforcement assessing primarily the effects of operant responding and comparable reward rates, and an operant procedure designed to test the effects of lever extension to prompt responding. These two control procedures involved comparable sensory-motor and motivational variables to those of the sustained attention task, but did not explicitly tax attentional processes. Performance of the sustained attention task was associated with a significant increase in cortical acetylcholine efflux, reaching a maximum of nearly 140%. Performance of the two control procedures was associated with significantly smaller (approximately 50%) increases in cortical acetylcholine release. This robust dissociation between attentional and control performance-associated increases in cortical acetylcholine release resulted, in part, from the elimination of the pre-task transfer of the animals into the operant chambers and the associated increases in acetylcholine release observed in previous studies. The present results support the hypothesis that demands on attentional performance, as opposed to the frequency of lever pressing, reward delivery and other task-related variables, selectively activate the basal forebrain corticopetal cholinergic system.

Acetylcholine↗
PubMed1992

Rat exploratory behavior controlled by intracranial self-stimulation improves the study of place cell activity.

This report is limited to the description of a procedure that should help to resolve the question whether firing fields of hippocampal place cells are relatively stable or modifiable by learning. Rats implanted with lateral hypothalamic electrodes for rewarding intracranial self-stimulation (ICSS) were trained to explore a circular open field (100 cm in diameter) while their locomotion was tracked by a computerized video system which also delivers ICSS whenever the animal's exploration has met certain experimenter defined criteria. The 3 following conditions were examined. (1) Homogeneous exploration of the entire field: ICSS was delivered after the animal repeatedly visited 5 equal segments of the field (central annulus and remainders of the 4 quadrants), entered randomly located circular areas of the field, and/or traveled a criterion distance. (2) Place field contingent reward or non-reward: ICSS was delivered when the animal entered a circular area (23 cm in diameter) corresponding to the place field after a previous visit to a similar area outside the place field. These conditions were reversed in the following task. (3) Delayed reward: ICSS was delivered when the animal entered the circular area and remained in it for 2 s. Each condition was tested for 600 s or until 50 ICSS were delivered. The behavioral procedures described make it possible to propose an experimental protocol that allows examination of the same place cell under conditions of homogeneous exploration with a segment condition or randomly distributed reward and under conditions with the place field signaling reward or non-reward. The delayed reward condition increases the accuracy of the target location and allows assessment of the phasic versus tonic nature of the place cell firing.

Animals↗
PubMed1981

Effects of phencyclidine, d-amphetamine and pentobarbital on schedule-controlled behavior in rats.

The effects of phencyclidine, d-amphetamine, and pentobarbital on responding maintained under a multiple fixed-interval (FI) 3-min fixed-ratio (FR) 30 schedule of food presentation were studied in rats. Phencyclidine (0.32-7.5 mg/kg) had a biphasic effect on overall response rate in both components; response rate increased and then decreased as the dose was increased. The FR was slightly more sensitive to the rate-decreasing effects of phencyclidine than the FI. The effects of d-amphetamine (0.1-7.5 mg/kg) on overall response rate were qualitatively similar to those of phencyclidine. The FI tended to be slightly more sensitive than the FR to the rate-increasing effects of d-amphetamine. Pentobarbital (1-18 mg/kg) produced little or no rate-increasing effects in the FR at low doses and decreased FR response rate at higher doses. In the FI, pentobarbital produced small increases in overall rate at intermediate doses while decreasing response rate at higher doses. The FR tended to be more sensitive than the FI to the rate-decreasing effects of pentobarbital. Unlike d-amphetamine and pentobarbital, phencyclidine produced smaller rate-increasing effects when the dose-effect curves were redetermined. Within the FI, the effects of phencyclidine and d-amphetamine on response rate were generally independent of the control rate of responding.

Animals↗
PubMed1979

The behavioral control of obesity: a descriptive analysis of a large-scale program.

Evaluated a behavoiral treatment program for 147 obese patients in a Weight Control Clinic. Weight losses during treatment averaged 11.01 pounds with large inter-S variability. Unlike past studies, patients continued to lose weight during a 6-month follow-up period. Weight loss was associated with age and initial degree of obesity, but other demographic and psychological variables failed to predict success in treatment. A critical examination of the attrition problem was carried out to determine the relationship between patient variables and the propensity to terminate treatment prematurely. Results demonstrate the utility of bahvioral treatment procedures for obesity, yet further research is needed to reduce attrition and to facilitate long-term maintenance of weight loss.

Adult↗
PubMed1992

Effects of self-generated rules on the development of schedule-controlled behavior.

College students responded under a multiple differential-reinforcement-of-low-rate 5-s fixed-ratio 8 schedule, with components alternating every 2 min. After 40 programmed minutes of acquisition and 12 min of maintenance, without notice, both schedules changed to extinction for 28 min. During acquisition, between alternations of the multiple schedule, some subjects were asked to develop rules describing the schedule contingencies. Other subjects were given these same rules between alternations, and a third group neither received nor were asked to develop rules. By the end of the acquisition phase, self-generated-rule subjects were more likely to show schedule-typical behavior than were subjects not asked to generate rules. The behavior of those given rules was similar to those asked to generate rules at the end of acquisition, but yoked-rule subjects acquired schedule-typical behavior at a quicker rate. By the end of extinction, during the period corresponding to the previous fixed-ratio interval, all no-rule subjects who had earned points during acquisition and maintenance were responding at a rate of less than 30 responses per minute. Only 3 of the 9 self-generated-rule subjects and 2 of the 5 yoked-rule subjects were similarly responding at this low rate. Results suggest that asking subjects to develop self-rules facilitates acquisition, but can retard extinction. Results also suggest that self-generated rules function similarly to external rules.

Adult↗
PubMed2006

Contribution of histamine type-1 receptor to metabolic and behavioral control of ventilation.

Histaminergic neurons in the hypothalamus are well documented as being involved in the control of autonomic functions, such as the balance of energy metabolism and circadian rhythm. We tested the hypothesis that an activation of the histamine type-1 (H1) receptor is required for the control of ventilation during the course of a day in free-moving mice. Ventilation, aerobic metabolism, and electroencephalogram were measured by a whole-body-plethysmograph, a magnetic-type mass spectrometry system, and a telemetry system, respectively, in H1 receptor-knockout (H1RKO) and wild-type mice. Both genotypes showed daily oscillations in minute ventilation (V(E)) and oxygen consumption (VO(2)), with greater values during the dark period compared to the light period. In the latter, H1RKO mice showed increased V(E) and CO(2) excretion (VCO(2)) relative to wild-type mice, and V(E) was comparable to the VCO(2) increase. However, there was no change in VO(2) in H1RKO mice, suggesting that differences in VCO(2) between genotypes are responsible for differences in V(E) during the light period. During the dark period, VCO(2) was elevated in H1RKO mice compared with WT mice. Because there was no difference in V(E), the ratio of V(E) to VCO(2) was reduced in H1RKO mice. Electroencephalogram results suggested that this might be due to a depressed arousal state in H1RKO mice because the ratio of delta to theta band power spectrum densities was greater in H1RKO mice than in wild-type mice. We concluded that histamine modulates ventilation by affecting metabolism and arousal state via H1 receptors.

Animals↗
PubMed1990

Evaluation of the pharmacological similarities between phenylpropanolamine and amphetamine: effects on schedule-controlled behavior.

In an effort to determine the degree to which the repeated administration of phenylpropanolamine (PPA) results in the development of tolerance to its disruptive effects on operant responding as well as cross-tolerance to the effects of acutely administered amphetamine, water-deprived rats were first trained on a fixed-ratio 5 (FR-5) schedule for water presentation. Dose-response curves for the effects of PPA and amphetamine (administered IP, 15 min presession) were then determined (ED50 = 35.0 and 2.6 mg/kg, respectively) followed by the chronic administration of 40.0 mg/kg PPA (administered IP, 15 min prior to each session). When responding returned to prechronic rates, the dose-response curves were redetermined for both PPA (ED50 = 220 mg/kg) and amphetamine (ED50 = 4.8 mg/kg). In a second set of rats, trained under similar conditions, it was observed that pretreatment with alpha-methyltyrosine (AMT, 100 mg/kg IP, 2 h presession) antagonized the disruptive effects of both PPA and amphetamine, whereas pretreatment with reserpine (0.31 mg/kg, IP, 12 h presession) antagonized the disruptive effects of PPA, but exacerbated the disruptive effects of amphetamine. In a separate experiment, the repeated administration of PPA 100 mg/kg or 200 mg/kg IP resulted in no long-lasting depletions of rat striatal dopamine, serotonin, or 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations. These observations indicate that PPA and amphetamine share a similar mechanism of action to the degree that cross-tolerance develops, but which is nonetheless dissociable with respect to their differential sensitivity to antagonists and their neurotoxic efficacy.

Amphetamine↗
PubMed1993

Acute neurobehavioral effects of co-inhalation of toluene and n-hexane on schedule-controlled behavior in rats.

Whether coexposure to toluene and n-hexane had any combined effects on the shock avoidance performance in rats was studied. Eighteen Wistar male rats with an avoidance rate of over 80% were selected and divided to three groups based on performance and body weight: (1) toluene, (2) n-hexane, and (3) toluene + n-hexane. Each group was exposed alternately first to air and then to a particular organic solvent for 4 hr at various concentrations (50, 100, 200, 400, or 800 ppm, in ascending order). The effects of each organic solvent were evaluated by comparing the performance of rats during and after exposure with their own performance under the sham exposure to air by three-way ANOVA. The main results were that (1) 200, 400, or 800 ppm toluene exposures increased lever press rates, (2) 50 ppm n-hexane exposure decreased lever press and avoidance rates in a transitory manner and 800 ppm n-hexane exposure increased the lever press rate, (3) the 50 ppm mixture (25 ppm toluene + 25 ppm n-hexane) decreased lever press and avoidance rates persistently during and after the 4-hr exposure and the 800 ppm mixture (400 ppm toluene + 400 ppm n-hexane) decreased lever press and avoidance rates unpredictably when compared to the results of 400 or 800 ppm of toluene or n-hexane alone. In conclusion, n-hexane showed narcotic effects at 800 ppm and modified the acute neurobehavioral effects of toluene in rats at 400 ppm toward unpredictable results.

Administration, Inhalation↗
PubMed1987

Effects of ethylketazocine and morphine alone and in combination with naloxone on schedule-controlled behavior in pigeons.

The behavioral effects of morphine and ethylketazocine were compared in pigeons responding under multiple fixed-interval, fixed-ratio schedules of food presentation. Both morphine and ethylketazocine produced dose-related decreases in rates of responding maintained under either schedule. Maximal effects of morphine were observed about 15-45 min after injection and typically lasted the entire session (about 60 min). Effects of ethylketazocine had a faster onset (maximal effects were observed within 15 min after injection), and shorter duration (effects diminished within the session). Ethylketazocine and morphine had similar potencies. Dose-effect curves for both drugs were shifted to a similar degree by naloxone.

Analgesics, Opioid↗
PubMed1988

Opioid receptor subtype-specific cross-tolerance to the effects of morphine on schedule-controlled behavior in mice.

Key-press responding of mice was maintained under a fixed-ratio (FR) 30-response schedule of food presentation. Successive 3-min periods during which the experimental chamber was illuminated and the schedule was in effect were preceded by 10-min time-out (TO) periods during which all lights were out and responses had no scheduled consequences. Intraperitoneal (IP) injections of saline or of cumulative doses of drugs were given at the start of each TO period. Successive saline injections had little or no effect on response rates, whereas the mu-opioid agonists morphine (0.1-10.0 mg/kg) and levorphanol (0.1-3.0 mg/kg), the kappa-opioid agonist ethylketazocine (0.03-3.0 mg/kg), the mixed mu-/delta-opioid agonist metkephamid (0.1-10.0 mg/kg), and the nonopioid dissociative anesthetic ketamine (1.0-100.0 mg/kg) generally produced dose-related decreases in response rates. Following chronic administration of morphine (100.0 mg/kg/6 h), tolerance developed to the effects of morphine on rates of responding. In addition, a comparable degree of cross-tolerance developed to the effects of levorphanol and metkephamid. On the other hand, there was no evidence of cross-tolerance to the effects of ethylketazocine or ketamine. These results are consistent with the evidence suggesting that different opioid agonists exert their behavioral effects through distinct classes of opioid receptors.

Animals↗
PubMed1986

The effects of some putative antidepressant agents on the schedule-controlled behavior of the pigeon.

Numerous "second-generation" antidepressants with pharmacological profiles and chemical structures different from those of the tricyclic antidepressants have recently been developed. We examined the actions of four of these compounds (mianserin, maprotiline, trazodone and fluvoxamine) on the responding of pigeons under two different multiple (mult) schedules of grain presentation (a mult fixed-interval (FI) 600-s fixed-ratio (FR) 30-response and a mult FI 200-s FI 200-s in which responding in one component was punished by intermittent presentation of a brief electric shock). The rate of FI 600-s responding was greatly increased by several doses of maprotiline and mianserin, which either did not affect or produced only small increases in the rate of FR 30 responding. Fluvoxamine and trazodone did not produce similar differential effects. Relatively low doses of maprotiline, mianserin and trazodone decreased the FI quarter-lives. Fluvoxamine only decreased the FI quarter-life at a dose that largely eliminated responding. Mianserin produced proportionally greater increases in the rate of punished FI 200-s responding than in the rate of unpunished FI 200-s responding. Selective effects on punished responding were not seen with maprotiline, fluvoxamine and trazodone.

Animals↗
PubMed1987

Tolerance to antinociceptive effects of morphine without tolerance to its effects on schedule-controlled behavior.

The development of tolerance to behavioral effects of morphine was investigated in rats that responded on a two-lever, multiple-trial, multiple differential-reinforcement-of-low-rate fixed-ratio (mult DRL FR) schedule of food presentation. Stable performances were maintained when sessions were conducted just twice per week. The effects of cumulative doses of morphine (1.0-8.0 mg/kg) or chlordiazepoxide (CDP; 4.0-32.0 mg/kg) were evaluated once per week; saline injections were given in the intervening sessions. The effects of saline and morphine on nociception were also evaluated in hot-plate tests conducted on the same subjects 15 min after selected operant sessions. Initially, morphine produced dose-related decreases in response rates and reinforcement rates in the DRL and FR components as well as significant increases in hot-plate response latencies. Following weekly administration of morphine (1.0-8.0 mg/kg) for 10 weeks, there was little or no tolerance to its effects on operant behavior. In contrast, complete tolerance developed to the antinociceptive effects of morphine. These results suggest that tolerance to various behavioral effects of morphine may be dissociated, and that the loss of reinforcement may be insufficient by itself to produce tolerance to effects of morphine on operant behavior. Additionally, whereas CDP initially produced only dose-related decreases in DRL and FR response rates, following weekly morphine the smaller doses of CDP (4.0-16.0 mg/kg) produced increases in response rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Effects of chronic d-amphetamine treatment on schedule-controlled behavior.

The effect of d-amphetamine added to the drinking water on the rate of conditioned lever pressing by rats was determined using fixed-ratio 30 (FR-30) and fixed-interval 2-min (FI-2) schedules of food presentation. After 32 days of gradual increase in drug concentration the average drug ingestion was 13 mg/kg/day. In tests with various doses of d-amphetamine injected before and after the chronic ingestion regimen, the rate-decreasing effects of d-amphetamine on FR responding were attenuated after chronic treatment, indicating development of a two- to three-fold tolerance. However, the rate-decreasing effect of d-amphetamine on FI responding was not altered by chronic ingestion. Since acute amphetamine treatment reduced the reinforcement frequency under the FR but not the FI schedule, these results are consistent with the hypothesis that a 'behavioral tolerance' will develop most readily to drug effects that decrease the frequency of reinforcement. Upon removal of d-amphetamine from the drinking water there was some increase in the rate of FR responding, but no change in FI responding.

Animals↗
PubMed1985

Effect of repeated intraperitoneal injections of soman on schedule-controlled behavior in the rat.

Intraperitoneal (IP) administration of the acetylcholinesterase inhibitor, soman (10-40 micrograms/kg), suppressed in a dose-related manner response rates in rats maintained under a multiple fixed-interval 50-s fixed-ratio 25 schedule of food delivery. Chronic administration of soman at weekly intervals resulted in tolerance to the response. When soman administration was separated by 2-5 weeks in individual rats, the suppressive effects of the agent again became apparent. Analysis of acetylcholinesterase activity revealed that enzyme inhibition was limited to gastrointestinal areas near the site of injection. There was no significant effect on brain acetylcholinesterase even following IP injection of doses which completely suppressed responding. The IP route may be useful for studying tolerance and other chronic effects of soman without producing generalized toxicity.

Acetylcholinesterase↗