Repeated Acquisition Task Research Articles

The mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) potentiates PCP-induced cognitive deficits in rats.

Recent studies have shown that metabotropic glutamate receptor 5 (mGluR5) can modulate N-methyl-D-aspartate (NMDA) receptor function in vivo. For example, the mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP) can potentiate PCP (phencyclidine)-evoked hyperactivity and PCP-induced disruptions in pre-pulse inhibition (PPI) in rats. To extend these previous behavioral findings and determine whether the mGluR5 antagonist MPEP can modulate the disruptions in learning and memory induced by PCP in rats. The effects of MPEP, alone and in combination with PCP, were evaluated in rats trained to perform a repeated acquisition procedure (learning) or a delayed non-matching to position (DNMTP) radial maze task (spatial memory). In the repeated acquisition task, MPEP (0-10 mg/kg, IP) dose-dependently decreased response rates but had no effect on response accuracy. In contrast, PCP (0.625-1.25 mg/kg, SC) reduced response rate and response accuracy in a dose-dependent manner. Although MPEP (10 mg/kg, IP) had no effect when administered alone, the mGluR5 antagonist potentiated the disruptions in learning induced by a low dose of PCP (0.625 mg/kg, SC). In the DNMTP maze task, MPEP (0-10 mg/kg, IP) had no effect on spatial memory, whereas PCP (1.25-2.5 mg/kg, SC) produced a dose-dependent disruption. MPEP (10 mg/kg, IP) potentiated the impairments in memory induced by PCP (1.25 mg/kg, SC). The mGluR5 antagonist, MPEP, potentiated the disruptions in learning and memory induced by PCP. These behavioral data extend previous behavioral findings and further suggest that mGluR5 can modulate NMDA receptor function in vivo.

Learning impairment caused by a toxin produced by Pfiesteria piscicida infused into the hippocampus of rats

Pfiesteria piscicida, an estuarine dinoflagellate, which has been shown to kill fish, has also been associated with neurocognitive deficits in humans. With a rat model, we have demonstrated the cause-and-effect relationship between Pfiesteria exposure and learning impairment. In several studies, we have replicated the finding in Sprague–Dawley rats that exposure to fixed acute doses of Pfiesteria cells or filtrates caused radial-arm maze learning impairment. Recently, this finding of Pfiesteria-induced learning impairment in rats has been independently replicated in another laboratory as well. We have demonstrated significant Pfiesteria-induced learning impairment in both the win-shift and repeated-acquisition tasks in the radial-arm maze and in reversal learning in a visual operant signal detection task. These learning impairments have been seen as long as 10 weeks after a single acute exposure to Pfiesteria. In the current study, we used a hydrophilic toxin isolated from clonal P. piscicida cultures (PfTx) and tested its effect when applied locally to the ventral hippocampus on repeated acquisition of rats in the radial-arm maze. Toxin exposure impaired choice accuracy in the radial-arm maze repeated acquisition procedure. The PfTx-induced impairment was seen at the beginning of the session and the early learning deficit was persistent across 6 weeks of testing after a single administration of the toxin. Eventually, with enough practice, in each session, the PfTx-exposed rats did learn that session's problem as did control rats. This model has demonstrated the cause-and-effect relationship between exposure to a hydrophilic toxin produced by P. piscicida and learning impairment, and specifically that the ventral hippocampus was critically involved.

Poster Sessions CP03: Trophic Factors. Effects of early post‐natal exposure of cerebral cortex to hyper‐IL‐6 on development and cognition in the CD‐1 mouse

Pro‐inflammatory cytokines, especially Interleukin (IL)‐6, are elevated in the brains and serum of very premature infants in association with perinatal infectious and hypoxic/ischemic insults. To determine potential adverse effects of IL‐6 on brain development, cross‐fostered litters of male cd‐1 mice were injected subcranially with hyper‐IL‐6 or vehicle at postnatal day (pnd) 4 and examined for alterations in functional landmarks of CNS development. No acute injury response was evident at 1–7 days following hyper‐IL‐6 injection as determined by glial morphology and RNase protection assays for acute response genes, ICAM‐1, iNOS, Mac‐1, A‐20, and EB‐22. In preweanling mice, reflex ontogeny and physical markers of development were not altered; however, exposed mice demonstrated increased over‐generalized motor responses (Fox Battery) leading to an overall impression of hyper‐reactivity and hyperactivity. At pnd 24 and 80, assessment of autonomic, sensory, and motor systems (Functional Observation Battery) showed persistence of hyper‐reactivity and hyperactivity. Learning and memory were assessed by passive avoidance (PA) at pnd 24 and by radial arm maze (RAM) in adults. Hyper‐IL‐6 exposure significantly impaired PA performance. RAM performance was similar between hyper‐IL‐6 and control groups in acquisition of win‐shift task but hyper‐IL‐6 animals showed deficits on repeated acquisition task. The persistent hyperactive, hyper‐reactive behavioral phenotype evident in hyper‐IL‐6 exposed mice appeared to interfere with performance on both learning and memory tasks, suggesting that early exposure of the developing brain to IL‐6 can have persistent adverse functional effects and raising additional concerns for effects of immune mediators in premature infants.

Effects of age and sex on the water maze performance and hippocampal cholinergic fibers in rats

We have examined if age-related deterioration of spatial memory and cholinergic innervation of the dentate gyrus is gender-specific. Aging progressively affected the performance of male and female rats in place discrimination version of the water maze task. On repeated acquisition task, only old males, but not old females, were significantly impaired relative to young and adult animals of both sexes. In parallel, we found that the age-associated reduction of the density of cholinergic fibers in the dentate gyrus was significantly more profound in old males than in age-matched females. These results suggest that, although male and female rats have an identical pattern of reference memory decline, impairment of the working memory and deterioration of the hippocampal cholinergic system are slower to develop in females than in males.

Insulin-like growth factor-1 ameliorates age-related behavioral deficits

Insulin-like growth factor-1 has been found to be involved in the regulation of several aspects of brain metabolism, neural transmission, neural growth and differentiation. Because decreased insulin-like growth factor-1 and/or its receptors are likely to contribute to age-related abnormalities in behavior, the strategy of replacing this protein is one potential therapeutic alternative. The present study was designed to assess whether cognitive deficits with ageing may be partially overcome by increasing the availability of insulin-like growth factor-1 in the brain. Fischer-344×Brown Norway hybrid (F1) male rats of two ages (four-months-old and 32-months-old) were preoperatively trained in behavioral tasks and subsequently implanted with osmotic minipumps to infuse the insulin-like growth factor-1 (23.5 μg/pump) or a vehicle, i.c.v. Animals were retested at two weeks and four weeks after surgery. Insulin-like growth factor-1 improved working memory in the repeated acquisition task and in the object recognition task. An improvement was also observed in the place discrimination task, which assesses reference memory. Insulin-like growth factor-1 had no effect on sensorimotor skills nor exploration, but mildly reversed some age-related deficits in emotionality. These data indicate a potentially important role for insulin-like growth factor-1 in the reversal of age-related behavioral impairments in rodents.

Behavioral Assessment of the Senescence-accelerated Mouse (SAM P8 and R1)

MARKOWSKA, A. L., E. L. SPANGLER AND D. K. INGRAM. Behavioral assessment of the senescence-accelerated mouse (SAM P8 and R1). Physiol Behav 64(1) 15–26, 1998. Senescence-accelerated mice (SAM P8 and R1) were behaviorally assessed in a cross-sectional study at 4 and 15 months of age. Behavioral measures included memory (place discrimination and repeated acquisition in a water maze), sensorimotor performance (turning in an alley, traversing bridges, wire rod hanging, and falls from a wire screen), psychomotor performance (open-field exploration), and emotionality (entries in a plus maze, grooming, and defecation in a plus maze and in an open field). In the water maze, aged P8 mice were impaired in place discrimination and in repeated acquisition tasks, demonstrating evidence of an age-related decline in spatial memory processing abilities. The demonstration of this impairment, however, was complicated by noncognitive factors, such as the tendency of many older P8 mice to float. Sensorimotor skill impairment was accelerated with age in P8 mice, but not in R1 mice, and this impairment was present despite the lack of age-related changes in body weight in P8 mice. Although P8 and R1 mice were not different in general activity at old age, P8 mice were substantially more hyperactive in an open field and in the plus maze than R1 mice when compared at young age. Independent of age, P8 mice demonstrated a reduction of anxiety-like behavior in the plus maze. Taken as a whole, the data suggest that although age-related behavioral alterations occur in the P8 mice, some of these changes are evident at 4 months of age. Thus, the behavioral abnormalities that exist not only represent an accelerated aging phenomenon but may also be considered a developmental pathology.

Repeated Acquisition of a Spatial Navigation Task in Mice: Effects of Spacing of Trials and of Unilateral Middle Cerebral Artery Occlusion

The working memory version of the Morris water escape task, the repeated acquisition task, consists of trial pairs in which an animal is started twice from the same start position. Animals have mastered this task when they need less time to find the platform in the second of the two trials. In this study, study, male C57BL mice were trained on this task with massed, spaced, or spaced delay trials in which there was a 90-min delay between the first and second trials of a pair. The mice trained with spaced trials learned the repeated acquisition task, whereas the mice trained with massed or spaced delay trials were not consistently able to do so. When the mice had reached a stable baseline performance, the middle cerebral artery (MCA) was occluded or the mice were sham-operated. Then, the effects of the MCA occlusion (MCA-O) on the performance in the repeated acquisition tasks were studied. MCA occlusion hardly affected the performance in this task, irrespective of the spacing condition of the trials, although surgery per se seemed to have a transient disruptive effect.

Molecular manipulations of extracellular superoxide dismutase: functional importance for learning.

Extracellular superoxide dismutase (EC-SOD) controls the availability of extracellular superoxide (O2.-), which is important for a variety of physiological pathways, including the primary means of inactivating nitric oxide (NO). The role of EC-SOD in neurobehavioral function has been until now unexplored. In the current studies, the phenotypic expression of genotypic alterations of EC-SOD production in mice were characterized for spatial learning and memory. Dramatic impairments in spatial learning in the win-shift 8-arm radial maze were seen in both EC-SOD knockout mice and EC-SOD overexpressing mice. The EC-SOD overexpressing mice were further characterized as having significant deficits in a repeated acquisition task in the radial-arm maze, which permitted the dissociation of long and short-term learning. Long-term learning was significantly impared by EC-SOD overexpression, whereas short-term learning was not significantly affected by EC-SOD overexpression. No systems have been shown to be importantly involved in learning and memory. This may be important in the current studies because EC-SOD has primary control over the inactivation of NO. We found that EC-SOD overexpressing mice were resistant to the cognitive effects of L-NAME (NG-nitro-L-arginine methyl ester hydrochloride), an NO synthase inhibitor. Decreased NO catabolism in these mice may have served to counter the effects of NOS inhibition by L-NAME. The current finding that EC-SOD levels that were either higher or lower than controls impaired learning demonstrates that the proper control of brain extracellular O2.- may be more vital than merely reduction of brain extracellular O2.- in maintaining adequate learning function.

Effects of neuroleptic and anticonvulsant drugs on repeated acquisition learning in microencephalic and normal rats.

Neuroleptic and anticonvulsant drugs are used to reduce the occurrence of aberrant behaviors, seizures, or both in individuals with mental retardation. However, their use may disrupt the learning of desired skills, and the extent to which anatomical (e.g., microencephaly) or biochemical abnormalities or both in such individuals alter the effects of drugs on learning is not known. In this study, the effects of neuroleptics and anticonvulsants on learning and performance in a repeated acquisition task in methylazoxymethanol-induced microencephalic and saline control rats were assessed. Thioridazine was more potent in microencephalic rats than in control rats in increasing errors and decreasing response rates. Clozapine was equally potent in both microencephalic and control rats in increasing errors and decreasing response rates. The effect of carbamazepine was biphasic in both rat groups: Low doses decreased errors and increased response rates, whereas higher doses did the opposite.

Effects of scopolamine on learning and memory in monkeys.

The effects of scopolamine were evaluated in monkeys responding under operant procedures designed to evaluate drug effects on learning and memory. In one procedure, responding was maintained by food presentation under a multiple schedule. One component of the multiple schedule was a repeated-acquisition task in which the discriminative stimuli for left- and right-key responses changed each session (learning). In the other component, the discriminative stimuli for responses were the same each session (performance). In both components of the multiple schedule, scopolamine produced dose-related decreases in responding; there was little evidence of differential rate-decreasing effects between components. Percent errors in learning were increased in a dose-related manner, whereas percent errors in performance were generally unaffected except at high doses, which also produced substantial decreases in response rate. These results suggest that acquisition is more sensitive to the disruptive effects of scopolamine than is performance. The second procedure utilized repeated acquisition and delayed performance as a technique to study the effects of scopolamine on memory. In this procedure, each session was divided into three phases: acquisition, delay and performance. After a 24-h delay, scopolamine had little or no effect on retention, accuracy or rate of responding. In contrast, after a 60-min delay, scopolamine decreased retention in a dose-related manner. These data suggest that scopolamine produces a greater disruptive effect on short (60-min) versus long (24-h) delays.

Comparison of the effects of full and partial allosteric modulators of GABAA receptors on complex behavioral processes in monkeys

Two baselines involving a repeated acquisition task were used to assess the effects of bretazenil, imidazenil, and triazolam. The first baseline was a multiple schedule of repeated acquisition and performance of conditional discriminations. In the first component, the subject acquired a four-response chain by responding sequentially on three keys in the presence of different combinations of colors and geometric forms displayed on a center key. Acquisition of the discrimination was defined by a decrease in errors as the session progressed. In the performance component, the four-response chain was the same each session. Incorrect responses in either component produced a 5s time out during which responding had no programmed consequence. The second procedure, which has been used to evaluate the effects of drugs on memory, involved the acquisition of a discrimination, followed by a 1h delay and a retest of the same discrimination to assess retention. Triazolam (0.32 and 0.56mg/kg) administered alone, produced dose-related decreases in response rate in each component. In addition, triazolam also produced a dose-related increase in percentage errors in acquisition with no effect in performance. Triazolam (0.32mg/kg) eliminated retention (0 percent savings) in the memory task. Bretazenil (0.1-5.6mg/kg) or imidazenil (0.1-1.8mg/kg) administered alone had little or no effect on either rate of responding or accuracy in either component. Furthermore, bretazenil but not imidazenil disrupted retention at the higher doses tested. The combination of imidazenil or bretazenil with triazolam produced dose-related attenuation of the disruptive effects of triazolam on both behavioral baselines. These data suggest that the disruptive effects of benzodiazepines on learning and memory may be a function of the intrinsic efficacy of these compounds at different GABA(A) receptor subtypes.

Age-Related Effects of the Nicotinic Antagonist Mecamylamine on Cognition and Behavior

Studies of the neurochemical pathology of Alzheimer's disease and Parkinson's disease reveal a severe and specific loss of central nicotinic cholinergic receptors. We have investigated the functional significance of this finding for cognitive functioning by studying the effects of the centrally active nicotinic antagonist mecamylamine. Single oral doses of mecamylamine were administered to 12 healthy young males and 15 healthy elderly subjects in doses of 5, 10, and 20 mg in a placebo-controlled, double-blind study. In both groups, the 20-mg dose caused a significant increase in errors in the learning condition of the Repeated Acquisition Task, producing a slower acquisition curve. There was no effect of drug on the performance component (retrieval of previously learned information). However, elderly subjects showed enhanced sensitivity to mecamylamine, with 10-mg dose producing significant impairment of learning not seen in the young normals. On a recognition memory task, there was an age-associated shift in response bias, with the elderly subjects becoming more liberal with increasing dose. Reaction-time measures suggested a dose-related slowing of reaction time on several tasks. Behavioral effects were minimal and physiologic effects were consistent with dose-related ganglionic blockade. These results indicate that acute blockade of nicotinic receptor function can produce measurable and significant cognitive impairment similar to some deficits seen in dementing illnesses, and that there is an age-related increase in sensitivity to nicotinic blockade.

Effects of age on water escape behavior and on repeated acquisition in rats

The standard water escape task in a circular pool measures predominantly spatial reference memory (RM). We first tested 3- and 24-month-old Wistar rats (WISW:Bor) in the standard task. The RM performance of the 24-month-old animals was impaired in comparison to that of the 3-month-old rats. In a second experiment, we compared the performance of 24-month-old rats with that of 3-month-old animals, using the repeated acquisition paradigm originally described by Whishaw (Physiology and Behavior, 35, 139-143, 1985; Behavioral Brain Research, 24, 59-72, 1987). In this paradigm, the decrease in escape latency from the first to the second trial within trial pairs measures predominantly spatial working memory (WM). The young rats acquired the task within the first sessions. In contrast, the 24-month-old animals did not acquire the task, even after 12 daily training sessions. It is not clear, however, whether the poor performance of the old rats on the repeated acquisition task reflects impaired WM or whether they did not acquire the procedural aspects of the task.

Behavioral effects of cocaine alone and in combination with ethanol or marijuana in humans

Intranasal cocaine (COC) and oral ethanol (ETOH) were administered to one group of seven research volunteers during daily experimental sessions. Following the determination of baseline subjective and performance measures, an ETOH cocktail (0, 19.4, 38.7 or 58.1 g of ETOH in lemonade) was consumed over a 10-min period. COC hydrochloride (4, 48, 96 mg) was inhaled 35-min after the start of ETOH drinking. In a separate experiment, seven research volunteers received intravenous cocaine and smoked marijuana (MJ), alone and in combination during daily experimental sessions. Following the determination of baseline measures, a 1-g MJ cigarette (0-2.7% delta 9-THC, w/w) was smoked and 13 min after the start of MJ smoking COC hydrochloride (0, 16, 32 mg) was given intravenously. ETOH increased simple-reaction time and decreased DSST trials. COC decreased DSST trials, increased incorrect responses on a list-learning task and attenuated the effect of ETOH on DSST performance. Only combinations of the high COC dose and the high MJ dose increased errors on a repeated acquisition task. Intranasal COC increased ratings of 'Stimulated,' and 'High' and LSD scores on the ARCI which were unaffected by ETOH. Increased ratings of 'Sedated' following ETOH alone were attenuated by intranasal (i.n.) COC. Intravenous COC and smoked MJ alone both increased ratings of 'Stimulated' and 'High.' There was a trend for combinations of i.v. COC and MJ to prolong these elevations. The results suggest that the interactive effects of COC in combination with ETOH or MJ, after acute administration, are subtle and in need of further analyses to better understand polydrug abuse.

Behavioral response to diazepam in a residential laboratory

Two groups of three healthy adult male volunteers without histories of sedative or other drug abuse participated in 15-day residential studies. Each day consisted of a private work period (10 am to 4:30 pm), during which subjects participated in traditional laboratory performance tasks, and a social period (5 to 11:30 pm), during which subjects had access to recreational activities available under social or private conditions. Tobacco cigarettes and food were available throughout each day (9 am to 12 pm). Diazepam (5 or 10 mg/70 kg) or placebo was administered orally twice daily in alternating three-consecutive-day intervals. Dosing order varied between groups. Diazepam had no effect on the total amount of time subjects spent in social conditions; however, the low dose increased verbal interaction, while the high dose decreased verbal interaction. Both doses disrupted performance on a second-order repeated-acquisition task but produced no effects on the other performance measures. Five of six subjects increased caloric intake following at least one dose, with the largest increases observed in subjects with the lowest baseline intake. Increases in subject reports of dose “Potency” and “Sedated” were also observed following the high dose. Diazepam doses routinely used in clinical settings influeced a variety of behaviors that are observed in the natural ecology, but not performance on accepted laboratory tasks.

Acute exposure to tris(2-chloroethyl)phosphate produces hippocampal neuronal loss and impairs learning in rats

Adult female. Fischer-344 rats were exposed to 275 mg/kg of tris(2-chloroethyl)phosphate (TRCP) by gavage. TRCP produced consistent signs of convulsive activity within 60–90 min after dosing and extensive loss of CA1 hippocampal pyramidal cells when examined 7 days after dosing. At the light microscopic level, toxic effects of TRCP on pyramidal cells in the CA3 and CA4 regions and on granule cells in the dentate gyrus were less severe than those on the CA1 cells. The seizure-related and neurohistological effects of TRCP were significantly attenuated by pretreatment with atropine or chlordizepoxide, suggesting that the hippocampal damage was related to the seizures produced by TRCP. In a second experiment designed to assess the potential health risk associated with TRCP, exposed rats were mildly impaired in the acquisition of a reference memory task in a water maze. However, TRCP-exposed rats were consistently impaired in performing a repeated acquisition task in the water maze. These data underscore the potential health risk associated with exposure to TRCP and support the conclusion that the hippocampus is intimately involved in spatial memory in rats.

Acute effects of d-amphetamine in a monkey operant behavioral test battery

The acute effects of d-amphetamine were assessed using a battery of complex food-reinforced operant tasks that included responding in delayed matching-to-sample (DMTS, n=6), conditioned position responding (CPR, n=7), progressive ratio (PR, n=8), temporal response differentiation (TRD, n=4), and incremental repeated acquisition (IRA, n=9) tasks. Performance in these tasks is thought to depend upon specific brain functions such as short-term memory and attention (DMTS), color and position discrimination (CPR), motivation to work for food (PR), time perception (TRD), and learning (IRA). d-Amphetamine sulfate (0.01–1.0 mg/kg IV), given 15-min presession produced significant dose-dependent decreases in the number of reinforcers obtained in each task. Response accuracy was significantly decreased at doses of 0.3 and 1.0 mg/kg for TRD and at 1.0 mg/kg for CPR when compared to saline injections. Accuracy was not consistently affected in the DMTS or IRA tasks. Response rates decreased or response latencies increased significantly at doses of 0.3 and 1.0 mg/kg in the PR and DMTS tasks. A dose of 0.1 mg/kg for the IRA and TRD tasks, 0.3 mg/kg for DMTS and 1.0 mg/kg for the CPR tasks significantly decreased percent task completed. Thus, the relative sensitivities of these tasks for detecting d-amphetamine behavioral effects were IRA = TRD > PR = DMTS > CPR. These results indicate that in monkeys, performance of operant tasks designed to model learning ability and time perception is more sensitive to the disruptive effects of d-amphetamine than is performance in tasks designed to model motivation, short-term memory and attention, which is more sensitive than tasks that model color and position discrimination.

Effects of opioids and phencyclidine in combination with naltrexone on the acquisition and performance of response sequences in monkeys

In each of three components of a multiple schedule, monkeys were required to emit a different sequence of four responses in a predetermined order on four levers. Sequence completions produced food under a fixed-ratio schedule. Errors produced a brief timeout. One component of the multiple schedule was a repeated-acquisition task where the four-response sequence changed each session (learning). The second component of the multiple schedule was also a repeated-acquisition task, but acquisition was supported through the use of a stimulus fading procedure (faded learning). In a third component of the multiple schedule, the sequence of responses remained the same from session to session (performance). Heroin, methadone, cyclazocine and phencyclidine each produced dose-related decreases in overall response rate. At high doses which produced equivalent rate-decreasing effects, cyclazocine and phencyclidine generally produced greater disruption of accuracy in the learning component than did heroin or methadone. Naltrexone 5.6 μg/kg shifted to the right by approximately 1 2 - log unit the heroin and methadone dose-effect curves, but produced little or no change in the cyclazocine dose-effect curves. At 56 μg/kg naltrexone completely antagonized both the rate-decreasing and error-increasing effects of heroin and methadone. The same dose of naltrexone tended to produce greater antagonism of the effects of cyclazocine on accuracy than on rate, which was shifted by only 1 4 - log unit. In contrast, naltrexone failed to antagonize the effects of phencyclidine on either rate or accuracy. Thus it would appear that while cyclazocine and phencyclidine produce similar disruptions in the accuracy of a discrimination, the effects of each are differentially sensitive to antagonism by naltrexone.

Effects of heroin, methadone, LAAM and cyclazocine on acquisition and performance of response sequences in monkeys

In each of three components of a multiple schedule, monkeys were required to emit a different sequence of four responses in a predetermined order on four levers. Sequence completions produced food on a fixed-ratio schedule. Errors produced a brief timeout. One component of the multiple schedule was a repeated-acquisition task where the four-response sequence changed each session (learning). The second component of the multiple schedule was also a repeated-acquisition task, but acquisition was supported through the use of a stimulus fading procedure (faded learning). In a third component of the multiple schedule, the sequence of responses remained the same from session to session (performance). At high doses, each drug tested produced essentially the same effect. In all three components, response rate was substantially decreased and percent errors increased. At lower doses, however, their effects differed. Heroin and methadone produced dose-dependent sporadic periods of pausing, but had little or no effect on the accuracy of responding. LAAM also produced sporadic periods of pausing, but its effects on accuracy were variable. In contrast, cyclazocine produced no such pauses in responding but rather decreased the local rates of correct responding in a dose-related manner. These same doses of cyclazocine increased percent errors in the learning component, but not in the faded learning or performance components. The results are generally consistent with the view that putative mu opioid agonists do not affect the accuracy of a discrimination in monkeys except at those doses which produce a substantial decrease in the overall rate of responding.

Alteration of response patterning by d-amphetamine on repeated acquisition in rats

The acute effects of d-amphetamine on response patterning in a repeated acquisition baseline were investigated with rats. Each session the animals acquired a different four-member response sequence on three levels. Each sequence (trial) completion produced a food pellet. Errors produced a brief timeout that was reset by responses made during the timeout. Acute doses of d-amphetamine (0.5–4.0 mg/kg) and saline were administered 30 min presession. The response patterns analyzed were perseverative responses to a single lever (runs), and a response to each lever in either a left-to-right or right-to-left direction (tranerses). The trial position, frequency, and lever location of error and timeout responses that occurred in the context of runs and traverses were studied. In contrast to control sessions, higher doses of d-amphetamine produced increases in the number of error and timeout responses emitted. The majority of these responses occurred as runs; traverse responding did not exceed control levels. Furthermore, the run error and timeout responding tended to occur early in the session and on a siingle response lever. The results are consistent with the view that d-amphetamine disrupts stimulus control and produces perseverative responding which may account for previous reports of disruption in repeated acquisition tasks following d-amphetamine administration.