Nicotinic-dopaminergic relationships and radial-arm maze performance in rats

Accurate performance on the radial-arm maze is dependent upon the integrity of nicotinic-cholinergic, muscarinic-cholinergic, and dopaminergic systems. Pharmacological blockade of these systems with mecamylamine, scopolamine, or haloperidol impairs choice accuracy in the maze. We have previously demonstrated that the performance deficit caused by muscarinic blockade is enhanced by coadministration of the nicotinic antagonist, mecamylamine, and is diminished by coadministration of the dopamine antagonist, haloperidol. In the present study, it was found that the choice accuracy deficit produced by nicotinic blockade is enhanced, not antagonized, by coadministration of haloperidol. Thus, although both nicotinic and muscarinic cholinergic systems are involved in radial-arm maze performance and antagonists of these receptors are additive in the deficits they cause, nicotinic and muscarinic interactions with dopaminergic systems are opposite in nature.     

Spatial memory and radial arm maze performance of rats

Rats were tested on an elevated radial maze for their ability to choose each of 17 different arms once without repeating any choices. The first experiment indicated that the animals performed well, choosing an average of more than 14 different arms in the first 17 choices. Subsequent experiments demonstrated that: (a) response patterns, general algorithms, or intramaze markings were not necessary for correct choices: (b) there was interference among choices within a test so that the probability of a correct response decreased as the number of choices increased; (c) there was no serial-order effect (primacy or recency); (d) animals tested in a procedure which did not require prior shaping showed no evidence of a general predisposition not to repeat choices. The results are discussed in terms of capacity, accuracy, and other characteristics of working spatial memory.     

Chronic nicotine and withdrawal effects on radial-arm maze performance in rats

Rats were tested for choice accuracy in an eight-arm radial maze during and after chronic administration of nicotine via subcutaneously implanted glass and Silastic capsules. Nicotine administration significantly improved choice accuracy relative to controls. The effect gradually became apparent over the first 2 weeks of exposure and persisted through the third week. Surprisingly, the significant facilitation of the nicotine-treated rats relative to controls continued for 2 weeks after the end of nicotine administration. No effects of nicotine were seen on choice latency or the strategy to make adjacent arm entries.     

Within-trial dynamics of radial arm maze performance in rats

The behavior of rats while solving a 12-arm radial maze was investigated using measures of response bias, choice latencies, and behavioral organization. Response bias decreased as a function of choice number, while the amount of time spent on the center platform between choices increased substantially during the last few choices. This increase in time between choices was largely accounted for by increases in investigatory behavior in the area of the doors leading to the arms. These data indicate that the processes involved in radial maze performance change over the course of each trial. As the choice sequence progresses, there is an increasing reliance on the use of information in memory, and a corresponding decrease in the use of response algorithms. In addition, the mean time taken to run down the chosen arm was shorter for correct choices than for incorrect choices, suggesting that arms are sometimes chosen despite a lowered expectation of finding food.     

Effects of the nicotinic receptor blocker mecamylamine on radial-arm maze performance in rats

Lesions of cholinergic neurons have been found by many investigators to impair choice accuracy in the radial arm maze. Because muscarinic receptor blockers, such as scopolamine, have also repeatedly been found to impair choice accuracy in the radial-arm maze, it has generally been thought that the critical effect of cholinergic lesions is the deafferentation of muscarinic receptors. The possible involvement of nicotinic receptors in the cholinergic bases of cognitive performance in the radial-arm maze has not been as well investigated. The present study examined the effects of the blockade of nicotinic receptors on performance of female Sprague-Dawley rats in the radial-arm maze. Acute administration of the the nicotinic receptor blocker, mecamylamine (10 mg/kg) was found to significantly impair radial-arm maze choice accuracy. This dose also caused a significant increase in response latency in the maze. The effect on choice behavior but not locomotor speed seemed to be due to the central effects of mecamylamine, because administration of the peripheral nicotine receptor blocker, hexamethonium (20 mg/kg), did not impair choice accuracy, even though it did increase response latency to a similar degree as the 10-mg/kg dose of mecamylamine. Lower doses of mecamylamine (2.5 and 5 mg/kg) did not impair choice accuracy. These results indicate that central nicotinic as well as muscarinic cholinergic receptors are involved with cognitive functioning.     

Effects of ketamine on tunnel maze and water maze performance in the rat

The NMDA receptor, which has been implicated in memory formation, is noncompetitively blocked by ketamine. The present study examines the effect of ketamine (0, 3, 6, 12, and 25 mg/kg body wt; ip) on tunnel maze and water maze performance in Wistar rats. In the hexagonal tunnel maze (HTM) high doses of ketamine (12 and 25 mg/kg) decreased locomotor activity. Moreover, ketamine induced perimeter walking (6, 12, and 25 mg/kg) and attenuated exploratory efficiency (25 mg/kg). When the HTM was converted into a modified six-arm radial maze, ketamine impaired short-term but not long-term memory. In the Morris water maze, rats injected with ketamine (12 and 25 mg/kg) acquired a spatial navigation task more slowly than controls. When the escape platform was removed, the drug-treated rats did not preferentially search for it in the area where the platform had been during the acquisition phase. However, when the escape platform was visible, no differences in the performance of ketamine-treated and control rats could be found. In summary, ketamine seems to attenuate some but not all forms of learning in the tunnel maze and it impairs the acquisition of a spatial navigation task.     

Sex differences and estropausal phase effects on water maze performance in aged rats

An age-related decline in memory has been reported in male rats; however, there are few studies that have addressed these changes in aged female rats. In young female rats, hormonal cycles influence behavior. By the age of 22 months most female rats have not had regular hormonal cycles for at least 9 months. In the current study we examined how the hormonal status (persistent estrus and pseudo-pregnant) of the aged (22-24 months) female rat (Long Evans) influenced performance on a spatial version of the Morris water maze and compared this to aged male rats. Aged females in persistent estrus showed better performance on the water maze than both aged females that were pseudopregnant and aged males. Thus, postestropausal hormonal status may influence the course of aging in females.     

Variable-ratio conditioning history produces high- and low-rate fixed-interval performance in rats

Four rats were exposed to an A-B-A-B series of 30 sessions each of variable-ratio 20 (A) and fixed-interval 30-s (B) schedules. Four other rats received 120 sessions of fixed-interval 30 s. The rats with a history of variable-ratio responding subsequently showed primarily high or low response-rate patterns on the fixed-interval schedule without evidence of classical scalloping (i.e., increased rates of responding throughout the interreinforcement interval), except infrequently in 1 rat. The rats exposed to only the fixed-interval 30-s schedule displayed the expected sequence of scalloping giving way to lower rate break-run or simply low-rate responding over time. This experiment shows that when naive rats are exposed to even a simple history of reinforcement (in this case, a variable-ratio 20), their subsequent fixed-interval performance is very different from comparable performance in naive rats, and might be said to be more similar to the responding of adult humans. The argument is made that care should be taken in comparing the fixed-interval performance of humans and nonhumans because humans have a complex history of reinforcement, whereas laboratory nonhumans are typically naive.     

Effects of scopolamine on repeated acquisition of radial-arm maze performance by rats.

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-of-curvature statistic, calculated for total errors, was used to quantify both the within- and between-session 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 within-session errors for all rats. Session times also were increased by scopolamine. An examination of within-session 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.     

The long-term effect of high- and low-rate responding histories on fixed-interval responding in rats

Tell rats were given extended lever-press training on a fixed-interval (FI) 30-s food reinforcement schedule from the outset or following exposure to one or two previous reinforcement schedules. For 4 rats the previots schedule was either fixed-ratio 20, which generated high response rates, or differential-reinforcement-of-low-rate 20 s, which produced low response rates. For 4 additional rats the extended training on FI 30 s was preceded by experience with two schedules: fixed-ratio 20 followed by differential-reinforcement-of-low-rate 20 s; or the same two schedules in the reverse order. Fixed-interval response rates were initially affected by the immediately preceding schedule, but after 80 to 100 sessions, all traces of prior schedule history had disappeared. The results also showed no long-term effect of schedule history on the interfood-interval patterns of responding on the FI 30-s schedule. These results support one of the most central tenets of the experimental analysis of behavior: control by the immediate consequences of behavior.     

Scopolamine interactions with D1 and D2 antagonists on radial-arm maze performance in rats

Recent evidence indicates that acetylcholine and dopamine play complementary roles in cognitive as well as motor functions. In our previous study, the dopamine receptor blocker, haloperidol, was found to attenuate the radial-arm maze choice accuracy deficit caused by the muscarinic acetylcholine receptor blocker, scopolamine. Haloperidol has activity in blocking both D1 and D2 dopamine receptor subtypes. The current study was conducted to determine whether this dopamine-acetylcholine interaction specifically involved D1 or D2 dopamine receptors. The D1 antagonist, SCH 23390, and the D2 antagonist, raclopride, were administered with a dose of scopolamine which caused choice accuracy deficits in the radial-arm maze. The scopolamine-induced deficit was reversed by SCH 23390, the D1 antagonist, indicating that D1 blockade alone is sufficient to reverse the amnestic effects of muscarinic blockade. There was no indication in this study that the D2 blocker, raclopride, had a similar effect. However, this does not mean that such an effect may not be present at other doses of raclopride or with other D2 antagonists. The present finding that D1 blockade counteracts scopolamine-induced cognitive dysfunction not only furthers the understanding of dopamine-acetylcholine relationships in cognitive function, it also suggests a promising direction for the development of treatments for cognitive dysfunction due to cholinergic loss.