Win-stay Task Research Articles

Drugs of abuse as memory modulators: a study of cocaine in rats

It has been proposed that drugs of abuse reinforce behavior partly, or wholly, because they facilitate learning by enhancing memory consolidation. Cocaine can clearly serve as a reinforcer, but its effect on learning has not been fully characterized. To explore the effects of different regimens of pre- and post-training cocaine administration on win-stay and object learning. Cocaine naïve and cocaine pre-exposed (30 mg/kg/day, × 5 days followed by 7 days drug-free) male Sprague-Dawley rats received cocaine (0, 1, 2.5, 7.5, or 20 mg/kg, i.p.) immediately following training on a win-stay task in a radial maze or following the sample phase of an object learning task. Win-stay performance was also assessed in tests of extinction and after a set shift. Post-training cocaine did not improve accuracy on the win-stay task and produced performance deficits at 20 mg/kg. These deficits were attenuated by prior cocaine exposure. There was indirect evidence of facilitated learning in extinction and set shift tests, but the effective dosage was different (2.5 and 7.5 mg/kg, respectively). Post-training cocaine produced dose-dependent improvements in object learning. Post-training cocaine administration can facilitate learning, but this effect is highly dependent on the dose and the type of task employed.

Effect of post-training administration of cocaine, diazepam and their combination on a win-stay task

According to the memory-enhancing hypothesis of addictive drugs, post-training administration of cocaine should enhance consolidation and thus facilitate learning. This hypothesis has not been tested in appetitive tasks reinforced by sucrose.The current study assessed the effect of post-training cocaine administration on the acquisition of a win-stay task, and modulation of this effect by co-administration of diazepam. Male Sprague–Dawley rats (n=63) were trained for 5days on a win-stay task performed on an 8-arm radial maze, and were administered cocaine (0, 2.5, 7.5 or 20mg/kg), diazepam (1mg/kg), or cocaine (7.5mg/kg)+diazepam (1mg/kg) immediately following each training session. Post-training cocaine caused dose-dependent impairments that appeared linked to the development of cocaine-induced sucrose taste avoidance and/or cocaine-induced anxiety. When it was attempted to modify these learned side effects of cocaine by co-administration of diazepam, it was observed that the drug combination slowed task completion and reduced overall number of nose pokes.These findings suggest that post-training cocaine can alter behavior on appetitive tasks through learned motivational deficits rather than through a selective action on memory consolidation. The implications for the memory-enhancing hypothesis of addictive drugs are discussed.

A triple dissociation of memory systems: Hippocampus, amygdala, and dorsal striatum.

This study investigated the respective roles of the hippocampus, the amygdala, and the dorsal striatum in learning and memory. A standard set of experimental conditions for studying the effects of lesions to the three brain areas using an 8-arm radial maze was used: a win-shift version, a conditioned cue preference (CCP) version, and a win-stay version. Damage to the hippocampal system impaired acquisition of the win-shift task but not the CCP or win-stay tasks. Damage to the lateral amygdala impaired acquisition of the CCP task but not the win-shift or win-stay tasks. Damage to the dorsal striatum impaired acquisition of the win-stay task but not the win-shift or CCP tasks. These results are consistent with the hypothesis that the mammalian brain may be capable of acquiring different kinds of information with different, more-or-less independent neural systems. A neural system that includes the hippocampus may acquire information about the relationships among stimuli and events. A neural system that includes the amygdala may mediate the rapid acquisition of behaviors based on biologically significant events with affective properties. A neural system that includes the dorsal striatum may mediate the formation of reinforced stimulus-response associations.

Win shifting in nectarivorous birds: selective inhibition of the learned win-stay response

A variety of nectarivorous species have demonstrated a bias to ‘win-shift’ (shift away from/avoid locations that have recently yielded food, as opposed to ‘win-stay’ behaviour where the animal returns to such locations). Since recently exploited ! owers contain no nectar, the win-shift bias is a candidate for an adaptive specialization of cognition. This bias tends to manifest as faster learning and/or better performance on a win-shift than a win-stay task. In standard win-shift/win-stay tasks (multiple two-phase trials where animals rst nd rewards in particular locations, and must subsequently avoid, or return to, such locations) noisy miners, Manorina melanocephala, and rainbow lorikeets, Trichoglossus haematodus, developed patterns of revisits/errors in the exploration phases that corresponded to the spatial contingency they experienced in the test phases: birds reinforced to shift revisited locations in the exploration phase that were unrewarded; birds reinforced to stay revisited rewarded ones. This was true even for birds that failed to shift or stay appropriately in the test phase itself. This suggests that the poorer performance of nectarivorous birds in win-stay than win-shift tasks may not be a consequence of an inability to learn the win-stay contingency. Our results suggest that these birds are equally sensitive to the win-shift and win-stay contingencies. This implies that, if the win-shift bias previously reported in nectarivorous birds is an example of a cognitive adaptation to the depleting nature of nectar, then the specially adapted mechanisms may have more to do with inhibition of the win-stay response than

Spontaneously hypertensive, Wistar Kyoto and Sprague–Dawley rats differ in performance on a win-stay task and a conditioned cue preference task in the water radial arm maze

This is the second in a series of studies that uses various configurations of the water radial arm to characterize the mnemonic systems in the spontaneously hypertensive rat (SHR) which is used frequently as a rodent model of attention deficit hyperactivity disorder. The first study indicated that SHR were impaired on a win-shift version of the task that required the use of spatial extra-maze cues to locate the hidden platform. The objective of the present study was to assess the performance of male SHR, Wistar-Kyoto (WKY) and Sprague–Dawley (SD) rats on (i) a win-stay version of the task that requires the use of proximal cue-based visual discrimination, and (ii) a conditioned cue preference task that is considered a measure of affective conditioning. In the win-stay task, SHR made fewer total errors than WKY and SD at the beginning of testing and after reversal of the value of the cues. In the conditioned cue preference task, SHR spent a similar amount of time in both arms; whereas, SD and WKY spent significantly more time in the arm with the cue that was associated with the platform. These findings indicate that SHR are not impaired on either the acquisition or reversal of a cued visual discrimination task in the radial water maze, but are impaired in terms of their performance on an affective learning task.

Effects of long-term ovariectomy and estrogen treatment on maze learning in aged mice

Spatial memory deficits occur earlier in female than male rodents as the animals age, and the cessation of estrous cycle has been suggested to play a role in this phenomenon. We examined the effects of long-term ovariectomy (OVX) and estrogen replacement therapy (ERT) with subcutaneous 17β-estradiol minipellets on maze learning in aged (24-month-old) female C57BL/6J mice using a win-stay task (1/8 arms baited) in the radial arm maze (RAM) and a position discrimination task in the T-maze. ERT was started 40 days before the behavioral tests both in gonadally intact (sham-operated) and OVX mice. The effect of early OVX on RAM performance was investigated using three different age groups (7, 11 and 24 months) with different OVX durations (4, 8 and 19 months, respectively). ERT reduced the number of reference memory errors in RAM in aged sham-operated and OVX mice, but unlike in young mice ( Heikkinen et al., 2002) it had no effect on working memory errors. Furthermore, OVX impaired the performance of aged mice in the T-maze. Comparison across the three age groups and three OVX durations indicated that the memory impairment induced by an early age OVX attenuates as the mice get close to their estropausal age.

Estrogen treatment improves spatial learning in APP + PS1 mice but does not affect beta amyloid accumulation and plaque formation

We investigated the effects of ovariectomy (OVX) and 17β-estradiol (0.18 mg per pellet) treatment on spatial learning and memory, hippocampal beta amyloid (Aβ) levels, and amyloid plaque counts in double transgenic mice (A/P) carrying mutated amyloid precursor protein (APPswe) and presenilin-1 (PS1-A246E). After OVX at 3 months of age, the mice received estrogen treatment for the last 3 months of their lifetime before they were killed at 6, 9, or 12 months of age. Estrogen treatment in A/P OVX mice increased the number of correct choices in a position discrimination task in the T-maze, and slightly improved their performance in a win-stay task (1/8 arms baited) in the radial arm maze (RAM). However, estrogen treatment did not reverse the Aβ-dependent cognitive deficits of A/P mice in the water maze (WM) spatial navigation task. Furthermore, ovariectomy or estrogen treatment in OVX and sham-operated A/P mice had no effect on hippocampal amyloid accumulation. These results show that the estrogen treatment in a transgenic mouse model of Alzheimer's disease (AD) improves performance in the same learning and memory tasks as in the normal C57BL/6J mice. However, the estrogen effects in these mice appeared to be unrelated to Aβ-induced cognitive deficits. Our results do not support the idea that estrogen treatment decreases the risk or alleviates the symptoms of Alzheimer's disease by inhibiting the accumulation of Aβ or formation of amyloid plaques.

Effects of persistent cocaine self-administration on amygdala-dependent and dorsal striatum-dependent learning in rats

The influence of persistent cocaine self-administration on learning and memory has never been evaluated. Our objective was to isolate the effects of contingently administered cocaine from those of its general pharmacological or non-contingent actions on multiple memory system functioning. A triad design was used to yoke passive cocaine and saline administration to the behavior of rats who were actively self-administering cocaine. Following 4 weeks of cocaine or saline exposure in 2-h sessions, six triads were tested in the amygdala-dependent conditioned cue preference task and dorsal striatum-dependent win-stay task in an eight-arm radial maze environment. Drug or saline sessions continued throughout task testing. Throughout task testing, rats actively and passively exposed to cocaine sustained a total daily intake of approximately 15 mg/kg. During the conditioned cue preference task, saline-exposed rats showed robust conditioned preference for a Froot Loops-paired cue. Rats actively and passively exposed to cocaine showed no evidence of conditioning despite normal exploration in the maze during preference testing. For the win-stay task, no significant differences were found among the three groups in terms of the number of sessions to acquire the task or task accuracy at criterion. Rats actively or passively exposed to cocaine, however, completed sessions more quickly than saline-exposed rats at criterion. These findings suggest that contingent and non-contingent cocaine administration similarly disrupt stimulus-reward functions of the amygdala, but do not disrupt stimulus-response functions of the dorsal striatum. This dissociation may relate to differences in the rate by which dopamine is cleared from these tissues following cocaine exposure or possibly to cocaine-induced devaluation of natural rewards, which influences stimulus-reward learning, but not stimulus-response learning.

Effects of Ovariectomy and Estrogen Treatment on Learning and Hippocampal Neurotransmitters in Mice

This study examined the effects of long-term estrogen treatment (sc 17β-estradiol minipellets) on learning in C57BL/6J female and male mice using a position discrimination task in the T-maze and a win-stay task (1/8 arms baited) in the radial arm maze (RAM). In addition, hippocampal monoamines and ChAT activity were measured at the end of the study and correlated to task performance. Female sham-operated (gonadally intact) and ovariectomized (OVX) mice were treated with estrogen either for 7 or 40 days before the behavioral tests and intact male mice for 7 days before the behavioral tests. In sham-operated mice the 40-day estrogen treatment improved RAM performance and in OVX mice both the 7- and 40-day estrogen treatments improved the performance in both maze tasks. The estrogen treatment also improved RAM performance in males. The hippocampal ChAT, NA, 5-HIAA, and DOPAC levels were decreased in OVX mice. Furthermore, the effects of estrogen treatment on the levels of hippocampal 5-HT and its metabolite 5-HIAA were different in sham-operated than in OVX mice. We could find no correlation between cognitive measures and neurochemical variables. This study gives new information about the effects of estrogen on learning and hippocampal neurotransmitters in mice.

High levels of estradiol disrupt conditioned place preference learning, stimulus response learning and reference memory but have limited effects on working memory

The present study investigated the effects of high levels of estradiol in female rats on four different radial arm maze tasks: the hippocampus-dependent spatial working-reference memory task; the prefrontal cortex–hippocampus dependent delayed win-shift task; the striatum-dependent cued win-stay task; and the amygdala-dependent conditioned place preference task. Ovariectomized female rats were injected daily with either 10 μg of estradiol benzoate or sesame oil vehicle ∼4 h prior to testing. In Experiment 1, treatment with estradiol disrupted learning on the spatial working-reference memory task by increasing the number of reference memory errors to reach criterion. In Experiment 2, treatment with estradiol had no significant effect on the delayed win-shift task. In Experiment 3, treatment with estradiol resulted in impaired performance on a striatum-dependent cued win-stay task. In Experiment 4, treatment with estradiol impaired the acquisition of a conditioned place-preference task. Taken together these findings suggest that high levels of estradiol inhibit reference memory, stimulus response learning, and amygdala-dependent appetitive conditioning while having little effect on working memory.

Spatial working memory improvement by an α 2-adrenoceptor agonist dexmedetomidine is not mediated through α 2C-adrenoceptor

1. Aged α 2C-adrenoceptor knockout and wild type mice were used to investigate whether α 2C-adrenoceptors are involved in mediating the beneficial effects of α 2-adrenoceptor agonist, dexmedetomidine, on spatial working memory. 2. A win-stay task in the radial arm maze was used to dissociate the effects of dexmedetomidine on working vs. reference memory. In addition, the animals were tested in simple response habit learning in the T-maze. 3. Knockout mice made more working memory errors after the change of the baited arm in radial arm maze, but after training reached again as accurate level of performance as wild type controls. Dexmedetomidine 5 and 10 μg/kg alleviated the increase in spatial working memory errors after the change of the baited arm in knockout mice. Knockout and wild type mice performed equally well in T-maze, and dexmedetomidine had no effect on this simple response learning. 4. The present results indicate that α 2-adrenoceptor agonists have a selective effect on spatial working memory not only in monkeys but also in mice. Further, this study confirms our earlier finding that the presence of α 2C-adrenoceptors is not necessary for the spatial working memory enhancing effect of α 2-adrenoceptor agonists.

Cognitive task performance after lidocaine-induced inactivation of different sites within the basolateral amygdala and dorsal striatum.

To determine whether discrete components of amygdaloid and striatal memory systems could interact to guide behavior in a radial arm maze, conditioned cue preference (CCP) and win-stay accuracy were examined after lidocaine inactivation of either the rostral (rBLA) or caudal (cBLA) basolateral amygdala, the lateral (lDST) or medial (mDST) dorsal striatum, or a control site in rats. CCP expression was blocked only after rBLA or cBLA inactivation. lDST inactivation prevented attainment of criteria win-stay performance, whereas rBLA and mDST inactivation delayed it. Control site inactivation did not influence performance in either task. These findings suggest that the amygdala works independently of other memory systems to regulate learned responses in the CCP task, the rBLA may work cooperatively with the lDST to guide behavior in the win-stay task, and the mDST is less critical than the lDST for attaining criteria performance in the win-stay task.

Effects of US devaluation on win-stay and win-shift radial maze performance in rats.

Previous studies have shown double dissociations between win-stay and win-shift radial maze learning in terms of their underlying neural substrates. To examine the content of the associations formed in the two tasks, the authors devalued the food unconditioned stimulus (US) by taste aversion to differentiate stimulus-stimulus(CS-US) and stimulus-response (CS-CR) learning. US devaluation was performed in rats that were over- or undertrained on the win-stay task. Devaluation substantially reduced food consumption on the maze but failed to disrupt choice accuracy, regardless of the amount of training. Devaluation did not affect latency in overtrained rats but did increase latency in undertrained rats. In the win-shift task, devaluation caused rats to reject the reinforcer, yet they continued to accurately win-shift, but with significantly longer latencies (Experiment 3). The results suggest that an S-R association may mediate performance after extended win-stay training. In contrast, a US representation appears to be recalled during early win-stay and win-shift performance.

Effect of intraventricular injections of dihydro-beta-erythroidine (DH,β E) on spatial memory in the rat

The analysis of the behavioral effect of the nicotinic acetylcholine receptor (nAChR) antagonists has been generally based on drugs which act at the associated ion channel. In contrast dihydro-beta-erythroidine (DH,β E) is a competitive antagonist at the nAChR. Using rats, DH,β E was injected intraventricularly prior to training in two spatial tests, the Morns Water Maze and a Win-Stay radial maze. In addition DH,β E 300 nmol was used to reverse the effect of (−)-nicotine on locomotor activity. In the Moms Water Maze DH,β E (300 nmol) disrupted memory of the platform location as measured by crosses of the area in a probe trial. At 300 nmol DH,β E showed no sensorimotor effects in a visible platform test. In the Win-Stay task there was a significant, dose dependent disruption of spatial memory. A dissociation of nicotine's effects on locomotor activity was observed, in that DH,β E 300 nmol was able to significantly attenuate (−)-nicotine enhancement of horizontal motor activity, but did not affect the initial reduction of vertical activity. Nicotinic processing of memory appears to be involved in these tests of spatial memory.

A triple dissociation of memory systems: hippocampus, amygdala, and dorsal striatum.

This study investigated the respective roles of the hippocampus, the amygdala, and the dorsal striatum in learning and memory. A standard set of experimental conditions for studying the effects of lesions to the three brain areas using an 8-arm radial maze was used: a win-shift version, a conditioned cue preference (CCP) version, and a win-stay version. Damage to the hippocampal system impaired acquisition of the win-shift task but not the CCP or win-stay tasks. Damage to the lateral amygdala impaired acquisition of the CCP task but not the win-shift or win-stay tasks. Damage to the dorsal striatum impaired acquisition of the win-stay task but not the win-shift or CCP tasks. These results are consistent with the hypothesis that the mammalian brain may be capable of acquiring different kinds of information with different, more-or-less independent neural systems. A neural system that includes the hippocampus may acquire information about the relationships among stimuli and events. A neural system that includes the amygdala may mediate the rapid acquisition of behaviors based on biologically significant events with affective properties. A neural system that includes the dorsal striatum may mediate the formation of reinforced stimulus-response associations.

Dissociation of hippocampus and caudate nucleus memory systems by posttraining intracerebral injection of dopamine agonists.

The effect of posttraining intracerebral injections of the indirect dopamine (DA) agonist d-amphetamine, the direct D2 agonist LY 171555, and the direct D1 agonist SKF-38393 on the acquisition of two 8-arm radial maze tasks were examined. On a win-stay task, a light cue signaled the location of food in 4 randomly selected maze arms on each trial, and animals were required to visit each of the lit arms twice within a trial. Posttraining intracaudate injection of d-amphetamine (10.0 and 15.0 micrograms), LY 171555 (2.0 micrograms), and SKF-38393 (5.0 micrograms) all improved win-stay acquisition in relation to saline-injected controls. In contrast, posttraining intrahippocampal injection of DA agonists had no effect on win-stay acquisition. On a win-shift task, rats were allowed to obtain food from 4 randomly selected maze arms, followed by a delay period in which they were removed from the maze. They were returned to the maze for a retention test in which only those arms that had not been visited before the delay contained food. Posttraining intrahippocampal (but not intracaudate) injection of d-amphetamine (5.0 micrograms), LY 171555 (2.0 micrograms), and SKF-38393 (5.0 micrograms) all improved win-shift retention in relation to saline-injected controls. The results demonstrate a double dissociation of hippocampus and caudate nucleus memory functions and show that posttraining injection of both D1 and D2 agonists modulate the memory processes subserved by both hippocampus and caudate nucleus.

Four-Choice Win-Stay Water Escape Acquisition by Rats

Rats were capable of acquiring a four-choice win-stay water-escape task. While preventing access to the incorrect choice sections on information runs affected the first choices made on test runs, it did not affect rate of acquisition.

Microinjection of dynorphin into the hippocampus impairs spatial learning in rats

The effect of hippocampal dynorphin administration on learning and memory was examined in spatial and nonspatial tasks. Bilateral infusion of dynorphin A(1–8) (DYN; 10 or 20 μg in one μl) into the dorsal hippocampus resulted in a dose-related impairment of spatial working memory in a radial maze win-stay task. Subsequent experiments found that acquisition of a reference memory task in the water maze was impaired by DYN injections (20 μg/μl) in the dorsal hippocampus, but not in the ventral hippocampus, and that this impairment could be blocked by naloxone. In a nonspatial task, posttraining DYN injections in the dorsal hippocampus had no effect on retention of step-through passive avoidance. These results suggest that dynorphin specifically interferes with spatial learning and memory, and that this effect is mediated by opioid receptors in the dorsal hippocampus.

Memory facilitation produced by dopamine agonists: Role of receptor subtype and mnemonic requirements

The role of dopamine (DA) receptor subtypes in the acquisition of two memory tasks in the 8-arm radial maze was examined. The receptors were manipulated with posttraining, subcutaneous injections of an indirect DA receptor agonist (D-amphetamine), a selective D2 receptor agonist (LY171555), and a selective D1 receptor agonist (SKF-38393). On a win-stay task (sensitive to caudate nucleus lesions) a light cue signalled the location of food in 4 randomly selected arms on each trial. Rats were given one trial per day and injected after training on day 5. D-Amphetamine (2.0 mg/kg) and LY171555 (2.0 mg/kg) improved performance relative to controls; however SKF-38393 (1–4 mg/kg) had no effect on the acquisition of win-stay behavior. On a win-shift task (sensitive to fornix/hippocampal lesions) a delay of 18 hr was imposed between the first 4 and second 4 choices; drugs were injected after the first 4 choices. D-Amphetamine (1.0 mg/kg) and LY171555 (2.0 mg/kg) significantly improved retention relative to controls. SKF-38393 (1–4 mg/kg) had no effect on win-shift retention. These results suggest that the memory-improving properties of DA agonists on tasks sensitive to both hippocampal and caudate lesions are mediated by the D2 receptor.

A comparison of win-shift and win-stay performance of rats in a radial arm maze

The purpose of the present experiment was to compare the performance of rats in a win-shift task and a win-stay task in a radial arm maze. To this end, three experiments were conducted using a variety of procedures. In general, the win-shift task required the rats to choose the unvisited arms and the win-stay task required the rats to return the visited arms. In Experiment 1, a free-choice memory recognition procedure was used, and in Experiments 2 and 3, a forced-choice memory recognition procedure was used. All three experiments showed that in the win-shift task, rats rapidly learned the task and performed well whereas in the win-stay task, the rats consistently showed a chance-level performance despite of the prolonged training. In addition to these findings, when the tasks were reversed (i.e. from the win-shift to the win-stay, and vice versa), the rats still showed a response strategy previously adopted (Experiment 3). These findings seem to be important in considering the characteristics of spatial memory in rats.