Robert N. Hughes

The value of spontaneous alternation behavior (SAB) as a test of retention in pharmacological investigations of memory

Because of its reliance on memory, the tendency for rats, mice and other animals to alternate successive choices of T- or Y-maze arms has assumed considerable popularity in pharmacological studies of spatial memory as a quick and simple measure of retention that avoids the need for extensive training and the use of conventional reinforcers. Two forms of this tendency have been utilized, namely two-trial and continuous spontaneous alternation behavior (SAB). However, as the behavior can also reflect drug-related changes in sensory/attentional, motivational and performance processes, SAB should not be unquestionably accepted as a measure of memory alone. While assessments of post-acquisition drug effects on longer term memory may be possible through the appropriate timing of drug administration, this is more problematic if SAB is used as a measure of shorter term memory. Even though SAB can be a useful index of responsiveness to novelty, its value as a measure of retention is less certain. In this latter respect, a possible alternative to SAB testing might be the recently developed form of the related procedure, responsiveness to change.

Behaviour of male and female rats with free choice of two environments differing in novelty

Abstract Male and female albino rats were individually observed for 15-min in an exploration box with access to a novel half and a similar half to which each subject had been confined for 24 hr prior to testing (i.e. the familiar half). A behaviour-sampling technique was used whereby it was noted at the end of every 10-sec period in which half of the apparatus the subject was and in what sort of activity it was engaged. The total number of exploratory units entered was also recorded. All rats were observed more often in the novel half than in the familiar half, but there was no significant difference between males and females on this measure. However, females were seen to be engaged in exploratory activity at the end of more 10-sec periods than males. Also, the proportion of exploratory to non-exploratory activity observed in the novel half was higher for females than for males. On the other hand males were seen to be engaged in grooming, eating or drinking and freezing behaviour more often than females. Decrements in locomotor and exploratory activity occurred for males during the 15-min observation period. There were also decrements in freezing and increments in grooming for both males and females and an increment in eating or drinking for males only.

Neotic preferences in laboratory rodents: issues, assessment and substrates.

Neotic preference refers to the extent to which animals prefer stimuli of differing novelty value. Degree of novelty is determined by within- and between-trials habituation and amount of temporal (novelty) and spatial change (complexity) in stimulation which in turn will determine the amount of curiosity-based approach (neophilia) or fear-based avoidance (neophobia) of novel stimuli. Tests of genuine neotic preferences enable direct assessments of responsiveness to temporal and spatial changes and include measurements of novel versus familiar locations (such as novelty-related location preferences), responsiveness to stimulus complexity (such as object exploration) and learning for exploratory rewards (such as light-contingent bar-pressing). Effects of brain lesions and peripherally administered drugs have implicated several brain areas and neurotransmitters that subserve memory, fear and reward in neotic preferences namely the hippocampus and ACh (memory), the amygdala, GABA and 5-HT (fear), and the mesolimbic DA reward system. However, more attention should be paid to the complexity of interactions between different brain and neurotransmitter systems and improvements in methodology before conclusions should be drawn about the neurobiological basis of neotic preferences.

Chlordiazepoxide modified exploration in rats.

Effects of 2.5, 3.75 and 5.0 mg/kg chlordiazepoxide on locomotion, rearing and preferences for novelty in rats were observed in an exploration box comprising a novel and a familiar half. Whereas an inverted U relationship between dose strength and locomotion was evident, rearing declined with increasing dosage. However, the two lower doses had little effect on preferences for novelty but 5.0 mg/kg produced a marked decrease to the point where the familiar half of the apparatus was preferred. It was concluded that estimates of drug effects on measures of locomotion or general activity are specific to those behaviours alone and do not necessarily relate to environmentally oriented exploration. Different views of the effects of drugs on exploratory behaviour might arise from the use of more valid indices, such as preferences for novelty.

Effects of caffeine, methamphetamine and methylphenidate on reactions to novelty and activity in rats.

Abstract Observations were made of the effects of three doses of caffeine, methamphetamine and methylphenidate on ambulation, rearing and novelty preferences in hooded rats. All three drugs produced inverted U-shaped dose-response curves for ambulation and U-shaped curves for novelty preference. Whereas both methamphetamine and methylphenidate increased rearing, this response was totally unaffected by caffeine. The results are discussed in terms of the classification of central-behavioural effects of the drugs and their modification of motor activity and exploratory behaviour.

Food deprivation and locomotor exploration in the white rat

Abstract 10 food-deprived rats and 10 non-deprived rats were observed for 15 minutes each in an exploration box allowing free choice between novel and familiar units. Although all subjects showed a preference for novelty, there were no significant differences in these preferences between the two groups as measured by the number of 10-second periods spent in the novel half of the box and by the percentage of novel units entered. However, the food-deprived rats entered a significantly greater total number of units. It was concluded that, contrary to earlier studies, food deprivation had not effected exploration of novelty but had possibly influenced activity of some origin other than strict exploratory tendencies.

The role of social isolation and sex in determining effects of chlordiazepoxide and methylphenidate on exploratory behaviour

Effects of two doses each of chlordiazepoxide and methylphenidate on exploration, locomotion and rearing were observed in isolated and grouped male and female rats. Sex of the animals determined the effects of both drugs on rearing, and of chlordiazepoxide on preferences for the novel half of an exploration box. Drug administration seemed to abolish initial sex differences on the former response. Locomotion of isolated and grouped animals was also differentially affected by chlordiazepoxide. These findings emphasised the need to take genetic and environmental factors into account when considering the effects of psychotropic drugs on exploratory behaviour.

Scopolamine induced changes in activity and reactions to novelty

The behavior of hooded rats was observed in an exploration box comprising novel and familiar halves following IP injections of 0.1, 0.25, 0.5, 0.75 or 1.00 mg/kg scopolamine or isotonic saline. Drug administration occurred after, rather than before, exposure to one of the alternative halves. All doses decreased reactions to the previously inaccessible novel half but decreases were greater for the 2 lowest doses. Rearing behavior was also suppressed by each dose whereas the number of apparatus cells entered (locomotion) was decreased by low doses but increased by high. The 3 behavioral measures showed declines in frequency during the course of each experimental session. However, low doses of the drug enhanced and high doses retarded these declines for rearing and cells entered. The study illustrated the difficulty in explaining data by unitary processes (such as attenuated habituation) when several behavioral indices and drug doses are employed within a single investigation.

SEX-AND AGE-DEPENDENT EFFECTS OF PRENATAL EXPOSURE TO CAFFEINE ON OPEN-FIELD BEHAVIOR, EMERGENCE LATENCY AND ADRENAL WEIGHTS IN RATS

Pregnant rats were provided with drinking water containing 0, 0.23 or 0.3 mg/ml of caffeine throughout gestation. These concentrations gave rise to daily doses of 0, 28 and 36 mg/kg. Open-field behavior and latencies to emerge from a darkened chamber were observed in offspring at regular intervals from 1 to 8 months after birth. The main results revealed increases in open-field locomotor and rearing activity with 28 but not 36 mg/kg/day. The opposite pattern characterized emergence latency. These changes were more typical of male rats particularly when older. Combining the present results with those of an earlier study by the authors strengthened the curvilinear trends observed and led to the conclusion that, low doses of prenatal caffeine increase activity and decrease emotionality. Higher doses may have the opposite effects to the point that the significant differences from control subjects reported earlier can occur. When 8 months old, female but not male rats prenatally exposed to 36 mg/kg/day of caffeine had significantly heavier adrenal glands than controls.

A review of atropinic drug effects on exploratory choice behavior in laboratory rodents.

Effects of atropinic drugs on various forms of exploratory-motivated behavior are reviewed. Whereas spontaneous alternation and preferences for novelty are reduced by such compounds, there are no clear-cut effects on reactions to complexity as in head-poke tests. However, novelty-reinforced learned behavior is consistently increased. In view of examples of drug-induced familiarity preferences, significant effects of peripherally acting atropinics, and a number of inconsistent findings, no single explanation based on interference with central cholinergic activity accounts for all findings. In addition to their highly suspect validity as measures of exploratory-motivated behavior, the effects of atropinic drugs on various motor activities are largely dependent upon other factors such as type of activity sampled, apparatus, dose, previous experiences, and strain of the subjects. However, in general, atropinics increase nonspecific motor activity and (in high doses) ambulation. Contrary to controls, animals exposed to novel stimuli under the influence of scopolamine or atropine remain highly responsive to the same stimuli when observed subsequently in an undrugged state. Similarities between the behavioral effects of brain lesions and atropinics support the septohippocampal axis as an important site of atropinic drug action for all of the choice and activity responses discussed. In view of the similar effects of a number of drugs with different central actions, the diversity of findings must be considered in the light of interactions between several neurotransmitters and behavioral mechanisms. Modification of one or more of several mechanisms such as habituation, memory, attention, and sensory acuity, as well as drug aversions, may be relevant when accounting for the effects of atropinics on various exploratory-motivated behaviors.