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PubMed1997

Substance P facilitates memory in goldfish in an appetitively motivated learning task.

The aim of this study was to investigate if the neuropeptide substance P (SP) can improve learning and memory in goldfish (Carassius auratus). Four groups of fish were trained for seven days to find food in one out of two compartments until discrimination was achieved. On the last training day, they were injected (intra-abdominal) with haloperidol or vehicle before the training, and with SP or vehicle immediately after the training session. Each group of fish received either: (1) vehicle+vehicle (n = 18); (2) vehicle + SP, (n = 20, SP 50 mg/kg); (3) haloperidol+ vehicle (n = 15, haloperidol 2 mg/kg); or (4) haloperidol+ SP (n = 14, haloperidol 2 mg/kg, SP 50 mg/kg). Twenty-four hours later, the time spent to find the food was recorded. Reversal training was done for four consecutive days after this post-injection test and the time spent to find the food was recorded again. The results indicate that only the group treated with vehicle + SP needed more time to reach reversal training than control fish (Mann-Whitney U-test, P = 0.0009). It is suggested that SP can enhance memory in fish and that this effect may have a dopaminergic mediation in discrimination learning task.

Animals↗
PubMed2005

The role of the dorsomedial striatum in instrumental conditioning.

Considerable evidence suggests that, in instrumental conditioning, rats learn the relationship between actions and their specific consequences or outcomes. The present study examined the role of the dorsomedial striatum (DMS) in this type of learning after excitotoxic lesions and reversible, muscimol-induced inactivation. In three experiments, rats were first trained to press two levers for distinct outcomes, and then tested after training using a variety of behavioural assays that have been established to detect action-outcome learning. In Experiment 1, pre-training lesions of the posterior DMS abolished the sensitivity of rats' instrumental performance to both outcome devaluation and contingency degradation when tested in extinction, whereas lesions of the anterior DMS had no effect. In Experiment 2, both pre-training and post-training lesions of the posterior DMS were equally effective in reducing the sensitivity of performance both to devaluation and degradation treatments. In Experiment 3, the infusion of muscimol into the posterior DMS selectively abolished sensitivity of performance to devaluation and contingency degradation without impairing the ability of rats to discriminate either the instrumental actions performed or the identity of the earned outcomes. Taken together, these results suggest that the posterior region of the DMS is a crucial neural substrate for the acquisition and expression of action-outcome associations in instrumental conditioning.

Animals↗
PubMed2003

Deficits in spatial learning and synaptic plasticity induced by the rapid and competitive broad-spectrum cyclooxygenase inhibitor ibuprofen are reversed by increasing endogenous brain-derived neurotrophic factor.

Cyclooxygenase (COX), which is present in two isoforms (COX1 and 2), synthesizes prostaglandins from arachidonic acid; it plays a crucial role in inflammation in both central and peripheral tissues. Here, we describe its role in synaptic plasticity and spatial learning in vivo via an effect on brain-derived neurotrophic factor (BDNF) and prostaglandin E2 (PGE2; both measured by Elisa). We found that broad-spectrum COX inhibition (BSCI) inhibits the induction of long-term potentiation (LTP; the major contemporary model of synaptic plasticity), and causes substantial and sustained deficits in spatial learning in the watermaze. Increases in BDNF and PGE2 following spatial learning and LTP were also blocked. Importantly, 4 days of prior exercise in a running wheel increased endogenous BDNF levels sufficiently to reverse the BSCI of LTP and spatial learning, and restored a parallel increase in LTP and learning-related BDNF and PGE2. In control experiments, we found that BSCI had no effect on baseline synaptic transmission or on the nonhippocampal visible-platform task; there was no evidence of gastric ulceration from BSCI. COX2 is inhibited by glucorticoids; there was no difference in blood corticosterone levels as measured by radioimmunoassay in any condition. Thus, COX plays a previously undescribed, permissive role in synaptic plasticity and spatial learning via a BDNF-associated mechanism.

Animals↗
PubMed1978

The effects of overtraining on mediational processes in elderly males.

To examine the effects of overtraining on mediational processes, 81 male residents (aged 55 or above) of a VA domicillary were tested using a two-choice discrimination task. Upon reaching criterion, the men were given, 0, 15, or 30 overtraining trials and then shifted to either a reversal, intradimensional, or extradimensional task. Analysis of the error scores resulted in a significant initial versus shift task main effect and type of shift by initial versus shift task interaction. Further analysis indicated no difference among the three shift groups for the initial task. However, in the shift task, the reversal group had significantly fewer errors than the other two groups who were not statistically different. Participants thus appeared to be mediationally sufficient when reversal and extradimensional tasks were compared, but mediationally deficient when intra- and extradimensional, and reversal and intradimensional tasks were contrasted. While overtraining had no significant effect, examination of the three way interaction suggested potentially facilitative effects of overtraining and a possible regression effect among participants not receiving overtraining.

Aged↗
PubMed2002

Spaced training facilitates long-term retention of place navigation in adult but not in adolescent rats.

Young and adult Long Evans rats were tested in the water maze according to two different procedures: half of the subjects were given one session of four trials a day for 6 days, whereas the other subjects had the same amount of training massed in 1 day. For both conditions, a 14-day retention interval was then introduced to test long-term memory. This was followed by a four-trial reversal session. All groups showed a significant learning curve, but escape latencies were shorter for the adult than for the young rats, without differential effect of the training procedure. A first probe trial (PT1) confirmed similar accurate short-term retention in all the groups. But unimpaired long-term memory was only seen in the adult rats trained with the spaced procedure. The young rats trained over 1 day also showed some retention of the platform location after 14 days, but not the other two groups. Reversal acquisition of the new platform location was rapid in the four groups. These results indicate that although accurate short-term spatial memory in the water maze is seen after a 1-day massed training in both age groups, unimpaired long-term retention is only observed in adult rats trained with 24-h inter-session intervals.

Aging↗
PubMed1999

Working memory, executive processes and the effects of alcohol on Go/No-Go learning: testing a model of behavioral regulation and impulsivity.

RATIONALE: Impulsivity is associated with increased risk for alcoholism. Alcohol also may increase impulsive behavior, although little is known about the processes underlying this effect. OBJECTIVES: This study tested a model proposing that the executive processes of working memory (WM) and conditional associative learning (CAL) modulate behavioral inhibition. Subjects had either a positive (FHP) or a negative (FHN) family history of alcoholism. Hypotheses were that alcohol would increase Go/No-Go impulsive responding but only in subjects with low working memory capacity (low-WM), low-CAL ability, or FHP for alcoholism. The model also predicted that WM and CAL modulate inhibitory responses to contingency reversal on a Go/No-Go task. METHODS: A Go/No-Go learning task with a midway contingency reversal was administered to 71 FHP and 78 FHN subjects when sober and after drinking one of two moderate doses of alcohol. WM (digits backward) and CAL (conditional spatial association task) were also assessed when sober. RESULTS: Alcohol resulted in more false alarms but only in low-WM subjects. Both WM and CAL modulated learning to inhibit behavior after contingency reversal, suggesting separate modulation mechanisms for WM and CAL. Subjects with low- capacity WM and subjects with low-capacity CAL ability had more difficulty learning response inhibition after contingency reversal. FHPs and FHNs did not differ in their response to alcohol. CONCLUSIONS: The results support our model of the modulatory role of WM and CAL in the ongoing regulation of behavioral inhibitory systems. The results also suggest that individuals with low capacity WM are more susceptible to alcohol's effect of increasing impulsive behavior, suggesting that alcohol reduces the capacity of working memory to modulate response inhibition.

Adolescent↗
PubMed1982

Cross-motivational effects of inescapable shock are associative in nature.

Exposure to inescapable shock interferes with the subsequent acquisition of an appetitive operant. This deficit may be due to either associative interference or activity reduction from the inescapable shock pretreatment. The relative importance of these two factors was examined by using an appetitive response choice discrimination procedure and concurrently measuring activity. Experiment 1 demonstrated separate associative and activity effects of inescapable shock, in that the animals exposed to inescapable shock made more incorrect responses than controls and were lower in activity. Experiment 2 demonstrated that these effects resulted from the uncontrollability of the shock, not from shock exposure per se. In Experiment 3, residual effects of inescapable shock were investigated by exposing animals to discrimination reversals. On these tests, inescapably shocked animals showed performance inferior to nonshocked controls, a result indicating that the effects of inescapable shock are not completely reversed by experience with contingent reward in the discrimination task. No evidence of an activity deficit was observed during this discrimination reversal. These results strongly suggest that associative factors play a more important role than activity reduction in mediating the effects of inescapable shock, at least when these are measured in an appetitive context.

Animals↗
PubMed1987

Noradrenergic rather than GABAergic processes as the common mediation of the antidepressant profile of GABA agonists and imipramine-like drugs in animals.

The present study was aimed at investigating in rats whether a common mechanism might underlie the reversal of depressive-like behaviors by classical antidepressants and by GABA agonists such as muscimol. Blockade of GABA transmission with picrotoxin (1 mg/kg IP) abolished the muscimol (0.5-1 mg/kg)-induced reduction of immobility in the swimming test and the reversal of escape failures in the learned helplessness paradigm. Conversely, picrotoxin was found not to reduce the efficacy of imipramine-like drugs in these same animal models. The combination of muscimol and tricyclics given at subeffective doses resulted in behavioral changes that can be accounted for by an additive interaction between these two classes of drugs. These data confirm the antidepressant-like profile of GABA agonists but suggest that it is unlikely that the primary antidepressant mechanism of conventional antidepressants involves GABA-A receptors. In the swimming test, prazosin (2 mg/kg), an alpha adrenoceptor blocker, antagonized the reduction of immobility produced by both muscimol and imipramine-like drugs. In the learned helplessness paradigm, penbutolol (0.25-0.5 mg/kg) and, though to a lesser extent prazosin, counter-acted the reversal of escape failures caused by muscimol and imipramine. On the basis of these data, it is tempting to speculate that increased transmitter outflow at noradrenergic receptors may be an essential component in the mechanism of action of imipramine-like drugs but also of GABA agonists.

Animals↗
PubMed1979

Effect of growth hormone on memory in mice.

In order to determine the effects of growth hormone (GH) on long term memory, two experiments were carried out, all involving a common paradigm. Mice were given massed training on a discrimination task and were injected with GH or control substances before and/or after training: retention was measured 4 weeks later. In Experiment 1, different groups of mice were injected with either GH or saline at five different time points relative to original learning (OL): 90, 30, and 5 min before, and 5 and 30 min after. The results showed a significant quadratic trend, in the form of a U-shaped curve for the GH-injected groups at retention. Maximal retention was observed at the 90 min pre-OL and the 30 min post-OL injection groups. Poorest retention was shown by the 5 min pre-OL injection group. In Experiment 2, GH, saline, and thyroid-stimulating hormone (TSH) were administered at 90 and 5 min pre-OL. In addition, a "state dependency" hypothesis was tested using additional groups of mice. The results again showed a severe drop in retention when GH was administered 5 min before OL; differences between the two pre-OL GH injection groups were less marked than in Experiment 1; TSH did not have the same action as GH; and finally, a state dependency interpretation was ruled out. Together the two experiments present results that indicate a selectively GH-induced suppression of memory when GH is administered in close proximity to OL. As the time lapse between the injection of drug and the learning task increases, the inhibitory effect on memory is reversed.

Animals↗
PubMed1968

Fading procedures and conditional discrimination in children.

A discrimination reversal task followed by a conditional discrimination problem was administered to children (age range 36 to 107 months). A fading procedure was used during the discrimination reversal training of some subjects and other subjects were trained by a traditional procedure. More subjects trained by the fading procedure performed without errors during training and more subjects in the traditional group solved the conditional discrimination problem.

Child↗
PubMed2006

The primate amygdala represents the positive and negative value of visual stimuli during learning.

Visual stimuli can acquire positive or negative value through their association with rewards and punishments, a process called reinforcement learning. Although we now know a great deal about how the brain analyses visual information, we know little about how visual representations become linked with values. To study this process, we turned to the amygdala, a brain structure implicated in reinforcement learning. We recorded the activity of individual amygdala neurons in monkeys while abstract images acquired either positive or negative value through conditioning. After monkeys had learned the initial associations, we reversed image value assignments. We examined neural responses in relation to these reversals in order to estimate the relative contribution to neural activity of the sensory properties of images and their conditioned values. Here we show that changes in the values of images modulate neural activity, and that this modulation occurs rapidly enough to account for, and correlates with, monkeys' learning. Furthermore, distinct populations of neurons encode the positive and negative values of visual stimuli. Behavioural and physiological responses to visual stimuli may therefore be based in part on the plastic representation of value provided by the amygdala.

Amygdala↗
PubMed1983

Recovery of function after brain damage: differences in aged rats?

Age at the time of brain injury is generally considered an important determinant in recovery of function. The implication is that older individuals show less recovery. Existing data challenge this common notion, but suggest differential effects of brain damage in aged subjects. To assess these differences old rats were trained on a two-choice brightness discrimination, subjected to visual decortication, and retrained with nonreversed or reversed reinforcement contingencies. A significant reversal impairment established that sparing of function in aged rats was similar to that in adult rats. However, a significant reversal X brightness interaction suggested that the progress of recovery of function in aged rats is influenced not only by what is spared but also by whether the expression of what is spared is consistent with or antagonistic to competing innate response biases.

Age Factors↗
PubMed1981

Early postnatal x-irradiation of the hippocampus and discrimination learning in adult rats.

Rats with X-irradiation-produced degranulation of the hippocampal dentate gyrus were trained in the acquisition and reversal of simultaneous visual and tactile discriminations in a T-maze. These experiments employed the same treatment, apparatus, and procedure but varied in task difficulty. In the brightness and roughness discriminations, the irradiated rats were not handicapped in acquiring or reversing discriminations of low or low-moderate task difficulty. However, these rats were handicapped in acquiring and reversing discriminations of moderate and high task difficulty. In a Black/White discrimination, in which the stimuli were restricted to the goal-arm walls, the irradiated rats were handicapped in the acquisition (low task difficulty) and reversal (moderate task difficulty) phases of the task. These results suggest that the irradiated rats were not handicapped when the noticeability of the stimuli was high, irrespective of modality used, but were handicapped when the noticeability of the stimuli was low. In addition, these results are consistent with the hypothesis that rats with hippocampal damage are inattentive due to hyperactivity.

Animals↗
PubMed1999

The effects of flumazenil on two way active avoidance and locomotor activity in diazepam-treated rats.

The present study was undertaken to determine the effects of chronic flumazenil treatment alone and simultaneously with diazepam on acquisition performance in an active-avoidance task and on locomotor activity in rats. Flumazenil (5, 10 and 20 mg/kg) and diazepam (0,5, 1.0 and 2.0 mg/kg) were administered intraperitoneally to rats before each daily training session for 5 days. The baseline of avoidance performance was set to approximately 50% and responses were expressed as acquisition rate. Locomotor activity of the rats was simultaneously recorded but only following the first training session. Diazepam decreased acquisition rate between the dose range used. Flumazenil had no effect on the acquisition rate of naive rats but reversed low dose diazepam-induced learning and memory impairment. Diazepam induced locomotor depression within the same dose range that decreased acquisition rate. Flumazenil had no effect on locomotor activity, but reversed the locomotor depressant effect of diazepam. The striking contradiction with previous data that flumazenil has no effect on learning-memory processing is discussed.

Animals↗