Rats repeatedly acquired the performance of selecting only the four baited arms in an automated eight-arm radial maze, with the arms containing food pellets randomly assigned prior to each session. During each 14-trial (trial: obtain all four pellets) daily session, the number of errors (selecting nonbaited arms or repeating arm selections) showed a within-session decline, and choice accuracy for the first four arm selections showed a positive acceleration across trials for all rats. An index-ofcurvature statistic, calculated for total errors, was used to quantify both the within-and betweensession improvement of performance. Scopolamine (0.03 to 0.3 mg/kg, ip), but not methylscopolamine (0.3 mg/kg), reduced the accuracy of the first four selections of each trial and increased total withinsession errors for all rats. Session times also were increased by scopolamine. An examination of withinsession accuracy showed only slight signs of improvement at the higher dosages of scopolamine. The results indicate that behavior in transition states maintained by reinforcement contingencies in the radial maze is similar to that maintained by extended chained schedules, despite the fact that some of the stimuli controlling behavior in the maze are absent at the moment behavior is emitted.
Drugs of abuse produce amnestic effects in humans and laboratory animals in a variety of tasks. Generally, only a few compounds have been examined in any particular procedure. It was the goal of the present studies to examine drugs of abuse of different pharmacological classes in rats responding under two behavioral schedules historically employed as experimental models of memory: spatial alternation and matching to position. One group of rats responded under a single-response spatial-alternation baseline with a 10-s delay and another group responded under a matching-to-position baseline with delay values of 3, 10 and 30 s. Performance under the spatial-alternation baseline was characterized by low variability and >90% accuracy. Under the matching-to-position baseline, saline control percent accuracy was >95% at 3 s, >85% at 10 s and >70% at 30 s. Under spatial alternation cocaine, d-amphetamine, pentobarbital, diazepam, phencyclidine, scopolamine and methscopolamine produced significant (P<0.05) effects on accuracy, whereas only cocaine, d-amphetamine, pentobarbital and phencyclidine disrupted accuracy under the matching-to-position baseline. These results suggest that spatial alternation may be a more sensitive baseline for determining drug effects on working memory in the rat.
The effects on memory of drugs of abuse from several pharmacological classes were examined in four adult male squirrel monkeys responding under a delayed matching-to-sample schedule of food presentation. Subjects were required to emit 20 responses on a sample key transilluminated by either a constant white or a flashing blue light. The twentieth response initiated a 3-second delay followed by presentation of two comparison stimuli. If a response was made to the key that matched the sample stimulus (correct match), a single food pellet (97 mg) was delivered. Pentobarbital (0.32-10 mg/kg), diazepam (0.1-5.6 mg/kg), phencyclidine (0.01-0.32 mg/kg) and cocaine (0.1-3.2 mg/kg) dose-dependently reduced accuracy of matching performance towards chance levels. Amphetamine (0.01-1.0 mg/kg) resulted in a small, but statistically significant, reduction in accuracy at a dose of 0.56 mg/kg, while 1.0 mg/kg completely suppressed responding. Analyses indicated that pentobarbital, diazepam and cocaine produced either position or color biases in responding, and in some cases these biases in responding were associated with decreases in accuracy. No such response biases were observed with phencyclidine or D-amphetamine. These results suggest that drug effects on working memory performance can, in some cases, be the result of non-mnemonic processes. Thus, they illustrate the importance of examining behavioral endpoints in addition to task accuracy when interpreting drug effects on working memory in laboratory animals.
ObjectiveTo examine biocompatibility and absorption profile of a poly (L‐lactide‐co‐D,L‐lactide) 70:30 nasal implant.MethodsIn an ovine model, 66 rod‐shaped absorbable implants were placed in 11 nasal dorsa. The sheep were sacrificed at 1.5 (N = 3), 6 (N = 3), 12 (N = 3), 18 (N = 1), and 24 months (N = 1). The nasal dorsum was harvested from each animal. Gross and histopathological examinations were performed.ResultsThere were no postoperative complications, signs of infection, or tissue rejection throughout follow‐up time points. Upon sacrifice, no abnormalities were identified during gross pathological examinations. The histology of the implant sites at all time points showed the implants were fully encapsulated through 12 months. The inflammatory reaction to the implants was minimal to mild at 1.5, 6, and 12 months. At 18 months the implant material was in the mass loss phase, being actively absorbed. During this phase, the inflammatory reaction within the fibrous connective tissue capsule reached expected moderate levels. By 24 months, the inflammatory reaction had diminished in most implantation sites and complete absorption of the rod implants was noted at some sites with nodular bundles of mature collagenized fibrous tissue replacing the implant, devoid of an inflammatory infiltrate.ConclusionBiocompatibility of the poly (L‐lactide‐co‐D,L‐lactide) 70:30 material was demonstrated when used as a nasal implant in the nasal dorsum ovine model. Absorption of the implant occurred approximately 18 to 24 months postoperatively, and the implant site was replaced with collagenized fibrous tissue.Level of EvidenceNA.
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