Holtzman and Harlan Sprague-Dawley rats: differences in DRL 72-sec performance and 8-hydroxy-di-propylamino tetralin-induced hypothermia

Several compounds were tested on the differential-reinforcement-of-low-rate 72-sec (DRL 72-sec) schedule, a behavioral screen to determine putative antidepressants; these compounds were evaluated in two outbred stocks of rats, Harlan and Holtzman Sprague-Dawley rats. A dose-response determination for the tricyclic antidepressants, imipramine and desipramine, the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor, fluoxetine, the 5-HT2 receptor antagonist, ketanserin, the 5-HT1A receptor agonist, (+/-)8-hydroxy-di-propylamino tetralin (8-OH-DPAT) and the dopamine releasing compound, amphetamine, were assessed in both rat stocks. The two stocks of rats differed in their baseline performance on the DRL 72-sec schedule. The Harlan rats had a higher reinforcement rate and a lower response rate than the Holtzman rats. In Holtzman, but not in Harlan rats, imipramine, ketanserin, fluoxetine and 8-OH-DPAT increased reinforcement rate and decreased response rate on the DRL 72-sec schedule, confirming previous studies. However, desipramine was the only drug to increase reinforcement rate and decrease response rate in both Holtzman and Harlan rats; in Harlan rats, drugs that primarily act upon the 5-HT system, imipramine, ketanserin, fluoxetine and 8-OH-DPAT, disrupted the DRL 72-sec performance and did not increase the number of reinforcements over baseline as was seen in Holtzman rats. Amphetamine disrupted DRL 72-sec performance in both Holtzman and Harlan rats in a similar manner. The hypothermic response to 8-OH-DPAT was also assessed in the two stocks of rats; Holtzman rats had a smaller decrease in core body temperature than Harlan rats. The observed behavioral and pharmacological differences between Holtzman and Harlan rat stocks may be genetically and/or environmentally mediated.     

Increased reactivity and impaired adaptability in operant behavior of adult mice given corticosterone in infancy.

Reports 2 series of tests of the operant behavior of 29 adult Swiss Albino male mice after early corticosterone treatment, which irreversibly decreases growth and DNA synthesis in the brain. Ss, paired with littermate controls, bar-pressed on continuous reinforcement at the same rate as controls but left more food uneaten; they responded at higher rates than controls during extinction and on a fixed-ratio-64 (FR-64) schedule. On 20-sec differential reinforcement of low rate (DRL), Ss again responded at higher rates and were less successful than controls in making a transition from FR-99 to 20-sec DRL. However, naive Ss were as efficient as controls on 20-sec DRL. Thus, after early hypercorticism, adult mice are hyperresponsive when working for food and show an impaired ability to adapt to a schedule change. (22 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of d-amphetamine on responding of squirrel monkeys maintained under second-order schedules of food presentation, electric shock presentation or stimulus-shock termination

The effects of d-amphetamine (0.01-5.6 mg/kg i.m.) were studied on lever pressing of squirrel monkeys maintained under various second-order schedules by a visual stimulus (S) that, with separate monkeys, was occasionally paired with the presentation of either food, electric shock or with the termination of a stimulus in the presence of which shocks occurred. Under one condition, the first response after 5 min produced a 3-sec stimulus change and the fourth stimulus change was followed immediately by food delivery, electric shock presentation or by the termination of a stimulus in the presence of which shocks occurred [fixed-ratio (FR); fixed-interval (FI) [FR 4 (FI 5-min:S)]. The effects of d-amphetamine were also studied under the food- and shock-presentation schedules when food or shock occurred only once, at the end of each session, after completion of 53n 3-min fixed-intervals all of which ended with a brief stimulus change [FR 10 (FI 3-min : S)]. Under a third condition, each thirtieth response produced the 3-sec brief stimulus (FR 30 : S) and the first FR 30 completed after 5 min elapsed produced the stimulus followed by food or, with separate monkeys, electric shock [FI 5-min (FR 30:S)]. Low to intermediate doses of d-amphetamine (0.03-0.3 mg/kg) generally increased and higher doses (0.56-5.6 mg/kg) decreased responding under all conditions. The effects of d-amphetamine on responding maintained by brief stimuli under different types of second-order schedules are generally similar, regardless of the type of reinforcing event or particular second-order schedule.     

Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity

The effects of various drugs were assessed in rats responding under a Differential-Reinforcement-of-Low-Rate 30-s (DRL 30-s) schedule. Atropine, scopolamine, and CEB-1957 (a new muscarinic blocker) increased response rate and decreased reinforcement rate, while methylatropine only decreased reinforcement rate. Physostigmine decreased response and reinforcement rates, when pyridostigmine had few effect on DRL responding. The irreversible acetylcholinesterase (AChE) inhibitors organophosphorus compounds (OPC) soman and sarin, injected at one-third of the LD50 did not consistently alter DRL performance, suggesting that they produce few behavioral effects in the rat when administered at subtoxic doses. Three oximes--pralidoxime, pyrimidoxime, and HI-6--decreased both response and reinforcement rates. Mecamylamine had few consistent effects on performance, and nicotine, d-amphetamine, diazepam, and the wakening drug modafinil increased response rate and decreased reinforcement rate. These two latter drugs also increased the number of very premature responses. These results, taken together, indicate that a DRL schedule is a useful tool to bring to light the existence of psychotropic effects of a drug. The explanation of drug-induced alterations of DRL performance, in terms of effects on cognition or on mood, is also discussed.     

Pretraining effects on performance of rats with hippocampal lesions.

Investigated the role of pretraining factors in the overresponding observed on differential-reinforcement-of-low-rate (DRL) schedules following hippocampal lesions. 24 Long-Evans hooded rats divided into unoperated Ss and Ss with large or small hippocampal lesions were given 10 or 20 days of continuous reinforcement (CRF) pretraining before exposure to a DRL 20-sec schedule. Either large lesions or extended CRF pretraining resulted in only a transient elevation in response rates, while the unique combination of a large lesion and extended pretraining was required for persistent overresponding on DRL. It is concluded that the overresponding produced by hippocampal damage is not solely a function of loss of hippocampal tissue but depends upon unique training conditions for its appearance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cued DRL training: Effects on the permanence of lesion-induced overresponding.

Attempted to determine the degree to which lesions in the septum and anatomically related structures result in the presence and/or permanence of overresponding on a DRL 20-sec schedule. Male Long-Evans hooded rats were given 15 days of training to determine the presence or absence of overresponding. Ss that overresponded were divided into 2 groups, with one receiving 15 days of cued DRL training and the other receiving 15 days of regular DRL training. Overresponding occurred in 60 Ss following lesions in septum, hippocampus, medialis dorsalis, and ventral thalamus pars dorsalis. While in effect, cued DRL facilitated performance in 8 controls and in operated Ss but did not facilitate performance when removed in septals. Exposure to the cued DRL allowed hippocampals to reduce responding and increase the frequency of obtained reinforcements. Lesions in medialis dorsalis and ventral thalamus led to an overresponding that disappeared with prolonged regular DRL training. Cued DRL training actually functioned as a time-out from DRL training. Variations in the permanence of the overresponding symptom according to lesion locus preclude identification of the lesion-induced dysfunction based solely on the presence or absence of overresponding. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

d-Amphetamine, operant history, and variable-interval performance

The effects of d-amphetamine on the bar-pressing of rats maintained under a variable-interval schedule of water reinforcement were examined as a function of the operant history of the subjects. One group of rats initially received 51 sessions of exposure to a fixed-ratio 20 schedule, while a second group received equivalent exposure to an interresponse-time-greater-than-12-sec schedule. Mean group response rate when stable was over ten times as high under the fixed-ratio schedule as under the interresponse-time-greater-than-12-sec schedule. Response rates of the two groups largely converged across 47 sessions of exposure to a variable-interval 60-second schedule, at which time response rates for both groups appeared stable. Acute administration of d-amphetamine sulfate similary affected mean response rates of both groups: A 0.25 mg/kg dose did not obviously affect rate, while doses of 0.5, 1.0, and 2.0 mg/kg produced dose-dependent rate decreases. These results indicate that the efficacy of operant history as a determinant of drug effects may be limited to circumstances where current contingencies do not exercise powerful and direct control over behavior.     

Immediate effect of septal area damage on DRL performance in the rat.

Investigated the immediate and long-term effects of septal area lesions on performance on a differential reinforcement of low rates (DRL) 10-sec schedule. Ss were 43 male albino rats. Septal area lesions produced immediate disruption of DRL responding in unanesthetized Ss, but cingulate area lesions or sham treatments did not. The induction of septal seizures without lesions produced only minimal disruption. For the first few testing sessions, Ss tested 7 days after receiving septal area lesions were indistinguishable in DRL performance from those tested immediately; the former, however, showed poorer recovery. It is concluded that neural or other changes requiring time to develop postoperatively are not essential to the disruption of DRL performance, but they may impede behavioral recovery. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Damage to hippocampus and hippocampal connections: Effects on DRL and spontaneous alternation.

A total of 162 male Sprague-Dawley albino rats were tested both pre- and postoperatively either on a DRL 20-sec schedule (Exp I) or for spontaneous alternation (Exp II). Selective lesions were produced in the hippocampus and its fiber connections. Performance of both behaviors was consistently disrupted by total fornix, medial fornix, and septum lesions, while neither behavior was significantly disrupted by postcommissural fornix or entorhinal cortex lesions. Anterior hippocampus lesions consistently disrupted only DRL performance, while neither posterior hippocampus nor lateral fornix lesions resulted in consistently impaired performance of either behavior. Data suggest a possible functional differentiation between anterior and posterior portions of the hippocampal system. (44 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of neonatal septal lesions on DRL performance in adulthood.

Reports 2 experiments on the influence of neonatal septal lesions on responding of 75 Long-Evans hooded rats trained on a DRL schedule in adulthood. Rats given septal lesions at 1 or 7 days after birth emitted a significantly higher number of responses and earned fewer reinforcements than did those given control electrode insertions. Thus, the inefficient performance on the DRL schedule, often observed after septal lesions in adulthood, does not depend upon the age of the S at the time of the lesion. Furthermore, operant training given at an early age (25-45 days) to Ss with neonatal septal damage did not facilitate performance when they were retrained in adulthood. In short, septal lesions at any age lead to permanent impairments of performance on a DRL 20-sec schedule. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of chlordiazepoxide, buspirone and cocaine on behavior suppressed by timeout presentation

Male Wistar rats were exposed to a two-component multiple schedule: a random-interval 30 s schedule of pellet presentation and a conjoint random-interval 30 s schedule of pellet presentation, random-interval 2 s schedule of timeout 10 s presentation. Once responding had stabilized subjects were injected intraperitoneally with vehicle, chlordiazepoxide (1-30 mg/kg), buspirone (0.1-4.2 mg/kg) or cocaine (1-30 mg/kg), 15 min before the start of the experimental session. Before drug administration, punished response rates were less than 30% of unpunished response rates for four of the six subjects, and 60% and 75% for the other two. Low doses of chlordiazepoxide (1 and 3 mg/kg) increased punished responding (range 25-300%), and slightly increased unpunished response rates (by 25% in all but one subject, whose rates increased by 75%). The higher doses of chlordiazepoxide (10-30 mg/kg) dose-dependently decreased response rates in both components. The lower doses of buspirone (0.1 and 0.3 mg/kg) either did not affect, or decreased response rates in both components of the schedule; the higher doses produced dose-dependent decreases. Low doses of cocaine (1, 3 and 5.6 mg/kg) did not affect response rates in either component of the multiple schedule, whereas higher doses produced a dose-dependent decrease in response rates, except for one subject whose punished response rates increased substantially. The behavioral effects of chlordiazepoxide and buspirone observed in the present experiment were similar to those observed in experiments in which response rates were suppressed by shock presentation.     

Collateral behaviors and the DRL deficit of rats with septal lesions.

Trained a total of 31 male Long-Evans hooded normal and septally-lesioned rats to lever press for food on a DRL 20-sec schedule in either a conventional operant chamber or 1 containing wood blocks and cardboard strips. The DRL behavior of normals trained in modified chambers was most efficient, and that of Ss with septal lesions trained in conventional chambers was least efficient. After 35 hr. of training, normals tested in conventional chambers and Ss with septal lesions tested in modified chambers did not differ significantly. Ss chewed the blocks and cardboard, and prevention of these collateral behaviors reduced DRL efficiency. Results show that colalteral behaviors facilitate the development of efficient DRL behavior and indicate that the DRL deficit of rats with septal lesions can be modified. (17 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Facilitation of instrumental behavior by a Pavlovian appetitive conditioned stimulus.

In Exp I, 16 New Zealand white rabbits were trained to perform an instrumental head-raising response for sucrose reward. A jaw-movement CR was established to a 2-sec CS by pairing it with sucrose; a control stimulus was unpaired with sucrose. Instrumental responding maintained by a VI 40-sec schedule was enhanced during 10-sec presentations of the paired, but not the unpaired, CS. Responding on a VR 15 schedule was unaffected except on trials on which the pre-CS baseline response rate was low; in such cases the paired CS caused a long-lasting acceleration of responding. Noncontingent presentation of the sucrose reinforcer itself briefly suppressed responding but had no long-term effect. In Exp II (6 Ss), a CS that had been conditioned at a 10-sec duration produced the same pattern of effects as in Exp I, indicating that facilitation resulted from CS presentation rather than from the frustrative effects of nonreinforcement of the CS. In Exp III (16 Ss), an inhibitory CS blocked facilitation by the excitatory CS but did not itself affect instrumental responding. (53 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

DRL performance, extinction, and secondary reinforcement: Role of appetitive value of food in mice with septal lesions.

Conducted 5 experiments with a total of 116 B6D2F-sub-1/J mice. Normal Ss and Ss with septal lesions were trained on a DRL 8-sec schedule for food reinforcement varying in incentive value. Dilution of diet increased the number of reinforcements received by Ss with septal lesions. In Exps II and III the effects of septal lesions on resistance to extinction after continuous reinforcement training and the strength of secondary reinforcement were investigated. Changes in reinforcement value modified the septal lesion effects in both cases. All 3 experiments demonstrated the alteration of the septal lesion effect through a change in the appetitive value of the reinforcement. Results suggest that one of the mechanisms by which septal lesions impair DRL performance is an enhancement of reinforcing properties of food. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of experience in acquisition and loss of tolerance to the effect of delta-9-THC on spaced responding

Albino rats were given extensive training in spaced responding, using a DRL 30 sec schedule of food reinforcement (only lever presses more than 30 sec apart were reinforced). All rats then went 12 days without behavioral testing. During this period half the rats received daily intragastric doses of delta-9-tetrahydrocannabinol (THC) and the rest equal volumes of the THC vehicle. On day 13, some rats received THC 3 hr before behavioral testing while others received only vehicle. The former showed a sharp increase in lever press rate over baseline levels, but the vehicle control rats were unaffected. The rats with 12 prior THC doses were no less affected than those with no previous drug history. Continued testing resulted in recovery of baseline performance within 5 sessions, again with no effect of previous drug history. Similar results were obtained with doses of 4 mg/kg and 16 mg/kg, though the drug's effects were more pronounced at the higher dose. These results demonstrate that performance in the drug state can be a far more important determinant of tolerance than mere exposure to THC. Drug administration was then suspended for 1 week. Rats that had become tolerant to 4 mg/kg THC were then redivided into 3 new groups. One group received daily doses of vehicle and DRL sessions, a second received DRL sessions without vehicle, and 1 group received neither vehicle nor DRL sessions for this week. Subsequent DRL testing after THC administration showed that only the groups receiving DRL sessions in the intervening week lost their previously acquired tolerance. Experience thus appears to play an important role in loss of tolerance to THC as well as in acquisition of tolerance.     

Factors which affect the relative contributions of ovarian and uterine arteries to the blood supply of reproductive organs in guinea pigs

The establishment and stability of the behavioral baseline for rats in relation to the schedule of differential reinforcement of low rate under water reinforcer (DRL 20 sec for water) were studied, with the following results: When the DRL value was gradually stepped up from 1 sec to 20 sec with the advance of the sessions from 1to 16, the establishment of the behavioral baseline was slower than when DRL 20 sec was applied from the start. The establishment of the baseline was clearly accelerated by the prolongation of the length of time for training in one session from 60 min to 120 min. The baseline remained highly stable without being affected by the intermittent administration (2-3 times a week) of methamphetamine and diazepam, each in doses from 0.06 to 1.0 mg/kg, and of caffeine and pentobarbital, each in doses from 1.2 to 20 mg/kg, or by the discontinuation of the test from 1 to 15 days. However, during the retraining period following the test discontinuation it was found that the baseline fluctuated for a long time due to the elimination of water deprivation. The baseline stability, once established, could be maintained through about 300 daily sessions, with only a slight dependence on the change in environmental conditions such as humidity, temperature, and the season.     

Some aspects of preference between immediate and delayed periods of reinforcement.

Two studies, with 6 homing pigeons, investigated an analog of the usual self-control paradigm by investigating choice between differently delayed reinforcer rates. Ss were trained on a concurrent-chain schedule in which the initial links (ILs) were equal VI schedules. The immediate terminal link (TL) consisted of an immediate 30-sec access to a VI schedule of food reinforcers, followed by a 30-sec blackout. The delayed TL consisted of an immediate 30-sec blackout followed by a 30-sec access to a VI food reinforcer schedule. Exp I comprised 3 parts, in each of which the TL VI schedules were varied. In Exp Ia, the IL responses that produced entries into both TLs were additionally reinforced with food; in Exp Ib, only the IL responses that produced entries into the delayed TL were additionally reinforced with food; and in Exp Ic, none of the IL responses that produced TL entries were additionally reinforced. When no TL entry responses were reinforced, IL response allocation was highly sensitive to variations in the TL schedules. Reinforcing entries into the delayed TLs (Exp Ib) decreased this sensitivity, and reinforcing entries into both TLs (Exp Ia) completely eliminated differential control by the TL reinforcer rates. Exp II varied the frequency of reinforcers for entries into the delayed TL and showed that even infrequent reinforcers strongly affected IL behavior allocation. Results are consistent with theories in which reinforcer value is a function of the summation of individual delays to reinforcing events. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age-related deficits in acquisition of a passive avoidance response.

In Exp. I, 80 male albino rats 10, 15, 20, 30, or 100 days old received a brief inescapable shock contingent upon making a step-off response. Step-off latencies increased for all age groups, but rate of learning was significantly faster in older Ss. Learning appeared to be based primarily upon punishment effects rather than general emotionality, since yoked Ss shocked after being placed directly on the grids did not acquire the avoidance response. Exp. II with 120 Ss employed 3 training conditions with independent groups 12, 15, 18, or 21 days old. The step-off response resulted in shock that was either: (a) escapable; (b) inescapable, 1-sec duration; or (c) inescapable, yoked duration. Younger Ss were again significantly inferior to more mature Ss. Escapable shock improved acquisition at 2 age levels, but the effect appeared to be more related to shock duration than to the response contingency. It is suggested that the requirement of withholding a punished response may represent a category of learning that is especially sensitive to maturational changes. (French summary) (16 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Separation of drug effects on timing and behavioral inhibition by increased stimulus control.

Impulsive behavior may represent, in part, a failure of behavioral inhibition (the ability to delay or inhibit a response). In this study, use of a multiple signaled–unsignaled differential-reinforcement-of-low-rates (DRL) 15-s schedule allowed examination of drug effects in conditions in which level of stimulus control differed. Results showed that whereas diazepam increased premature responding during signaled and unsignaled DRL components, amphetamine and Δ?-tetrahydrocannabinol increased premature responding primarily during unsignaled components when timing was necessary for efficient performance on the task. In contrast, primozide and desipramine increased long-delay responses across both components, resulting in longer mean interresponse times. Collectively, these results suggest that the use of different levels of stimulus control may aid in separation of drug effects on timing and other behavioral processes, including behavioral inhibition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Developmental analysis of behavioral dysfunction in rats with septal lesions.

At 7 days of age, 48 male Long-Evans hooded rats received lesions of the septal nuclei or control operations. Ss then received 30 hrs of training on a DRL 20-sec schedule for 1 hr/day beginning at either 27 or 96 days of age. At 126 days of age, all Ss received 10 additional training sessions. After operant testing, all Ss received 10 additional training sessions. After operant testing, all Ss were tested on spontaneous alternation, spatial reversal, and passive avoidance. Results indicate that on a DRL 20-sec schedule Ss that received lesions of the septum neonatally and were tested at different ages performed in a similar manner. Approximately 50% of the Ss with lesions of the septal nuclei reached efficiency levels comparable with those of normal controls. When tested for retention, these efficient Ss still performed similarly to normal Ss. Ss with septal lesions were facilitated in the acquisition of a spatial habit, were deficient in spatial habit reversal, were less likely to demonstrate spontaneous alternation, and were deficient in passive avoidance. It is concluded that neonatal lesions of the septal nuclei produce permanent behavioral impairments on a diversity of measures and that, although juvenile animals with limbic system damage often manifest behaviors different from adult Ss, the difference is not evident during operant testing (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)