Roman High Avoidance Research Articles

The current status of two sublines of the Roman High and Low Avoidance strains.

Experiments are described which assess the behavioral status of two sublines of the Roman High and Low Avoidance strains which have been maintained by brother x sister mating without selection at the Institute of Psychiatry, University of London. The strains demonstrate significant differences in the avoidance behavior for which they were originally selected. However, the Low Avoiding strain did show some high-scoring individuals and a degree of selection pressure was consequently applied to this line. The results of this selection and the performance of these strains in an open field are reported. The data are discussed in the light of a recent report that other sublines no longer display differences in avoidance conditioning.

Differential response to cholinergic stimulation in psychogenitically selected rat lines.

Male and female rats of two lines psychogenetically selected for bipolar extremes in shuttle box avoidance were evaluated for tremor, salivation, chromodacryoorhea, and hypothermia following treatment with the muscarinic cholinergic agonist oxotremorine. Roman Low-Avoidance (RLA/Verh) rats exhibited more pronounced oxotremorine-induced tremor, chromodacryorrhea, and hypothermia than Roman High-Avoidance (RHA/Verh) rats. There was a sex difference only for a chromodacryorrhea response, with females exhibiting a greater response following oxotremorine than males. In a subsequent experiment using female rats of both rat lines, it was demonstrated that pre-treatment with the cholinergic antagonist scopolamine blocked oxotremorine-induced tremor, salivation and chromodacryorrhea responses in both rat lines and reduced the hypothermic effect observed in RLA/Verh rats (but not the much weaker hypothermia found in RHA/Verh rats) after oxotremorine injection. Pretreatment with the peripherally active cholinergic antagonist methscopolamine significantly reduced oxotremorine-induced salivation and chromocacryorrhea and somewhat decreased tremor and hypothermic responses in both rat lines. These results stand in contrast to the results of earlier research in which RHA/Verh rats exhibited greater behavioral depression in a tunnel maze than RLA/Verh rats following cholinergic manipulations. In view of evidence that these rat lines do not differ in number of muscarinic brain receptors, the present results may be due to genetic differences in other aspects of cholinergic neurotransmitter function, differences in the function of other neurochemical systems, or differences in the absorption, distribution, or metabolism of oxotremorine.

Microstructural analysis of chlordiazepoxide's effects on food preference behavior in Roman high-, control- and low-avoidance rats

The effects of chlordiazepoxide (CDP) on feeding performance and on rearing activity were investigated using a food preference test in three Roman strains: Roman Low Avoidance (RLA), Roman Control Avoidance (RCA), and Roman High Avoidance (RHA). The aims of the study were to assess the responses of the three strains to a free choice of familiar and novel foods following a period of food deprivation, and to answer the important psychopharmacogenetic question of whether or not the strains would display differential responsivity to CDP challenges. No strain differences were discovered in relation to the latency to begin feeding, the response to familiar food, or the frequency of rearing in the 10 min food preference test. However, clear differences did emerge in relation to the animals' responses to novel foods. In contrast to the RCA and RHA lines, RLA rats sampled a greater variety of the available foodstuffs, and devoted a greater duration to the consumption of novel foods. Despite previous reports that under conditions of mild stress, RLA animals display greater emotionality, there was no evidence from the present study to show that RLA animals were more neophobic (a possible index of emotionality) than the other two Roman lines. Indeed, the evidence clearly suggests that RLA animals may under certain circumstances pay greater attention to novel cues. CDP treatments produced reductions in rearing, reductions in eating latency, and strongly potentiated the time devoted to feeding. Effects of CDP treatments on familiar and novel foods were dissociable. CDP at 10 mg/kg reliably increased the novel food feeding duration, an effect occurring mainly within the first 5 min of the test. CDP at 5 and 10 mg/kg reliably increased familiar food feeding duration, but this effect was in evidence for both halves of the test. Despite the multiple significant effects of CDP treatments in the food preference test, as well as the capacity of the test to demonstrate selective behavioral differences between the Roman lines, no evidence emerged for a significant interaction between strains and CDP treatments. So far as the behaviors measured in the food preference test were concerned, there was no differential sensitivity separating the Roman strains in response to CDP treatments.

Brain octopamine and strain differences in avoidance behavior

According to recent research, a significant relationship seems to exist between brain contents of p-octopamine and two-way avoidance responding in rats. Levels of this amine in hypothalamus and brainstem are higher in rats from the Roman High Avoidance (RHA) strain than in rats from the Roman Low Avoidance (RLA) strain. Intracerebroventricular administration of p-octopamine facilitates avoidance responding. The present paper reports the behavioral and neurochemical effects of p-octopamine administration on rats from the Roman strains. This treatment has no significant effect on cerebral levels of catecholamines, but it temporarily suppresses the strain differences in p-octopamine levels. In parallel, it also suppresses the strain differences in two-way avoidance conditioning, its facilitatory effect being much greater in RLA than in RHA rats. Avoidance behavior appears to be a useful model for the study of octopamine functions in the mammalian brain.

Hyponeophagia in the Roman rat strains: Effects of 5-methoxy-N,N-dimethyltryptamine, diazepam, methysergide and the stereoisomers of propranolol

The effects of 5-MeODMT (2.5 mg/kg), diazepam (1 mg/kg), methysergide and the stereoisomers of propranolol (6 mg/kg) on hyponeophagia were studied in both sexes of the Roman strains of rats, selectively bred for acquisition of a two-way conditioned avoidance response. Diazepam, methysergide and 1-propranolol increased feeding in a novel environment whilst 5-MeODMT decreased it and d-propranolol was inactive. Several strain differences in drug responsiveness occurred, the Roman Low Avoidance subjects being most sensitive to all drugs tested as well as being most neophobic. A sex difference in 5-MeODMT sensitivity was also found, female rats of the Roman High and Control Avoidance strains being more sensitive than males. The findings are discussed in connection with differences in arousal and biochemical parameters between these strains.

Two-way avoidance behavior of the Roman rat strains following brain lesions

Rats of the Roman strains, Roman High Avoidance (RHA), Roman Low Avoidance (RLA) and Roman Control Avoidance (RCA) were submitted to 5 conditioning sessions in a two-way shuttle box; the sessions were separated by a 24 hr-interval. Two indices were computed: a within-session progression index W and an inter-session progression index I. Index W was comparable in all three strains; index I was strongly negative in RLA and equal to zero or slightly positive in RHA rats. Lesion of the hippocampal commissure (HC) significantly facilitated CAR acquisition in RLA by making index I less negative: performances of RCA and RHA rats were unaffected. Lesions of the centro medianum parafascicularis nuclei of the thalamus (CM) significantly impaired acquisition of CAR in RCA and RHA by making index I more negative; performances of RLA rats were unaffected. Neither lesion altered index W. These results support the “freezing hypothesis” in the explanation of the Roman strain differences. They are in agreement with recent data on the emotional characteristics of the Roman strains and on the role of octopamine in avoidance behavior.

Rapid acquisition of two-way active avoidance in inbred Roman low avoidance rats.

Two inbred strains of rats, derived from the Roman High Avoidance and Roman Low Avoidance selection lines, were tested for performance on the two-way active avoidance task which had been used during selection. Both inbred strains rapidly acquired the avoidance response and showed nearly perfect avoidance from trial 40 through trial 50. Probably, genes responsible for the low avoidance performance in the RLA strain disappeared during inbreeding.

Regional distribution of [ 3H]imipamine binding sites in the CNS of Roman high and low avoidance rats

The high affinity binding of [ 3H]imipramine to membranes was compared in 7 brain regions from two psychogenetically selected rat lines (RHA/Verh, RLA/Verh). A significantly higher binding in RHA/Verh rats, as compared to RLA/Verh rats, was found in cortex and striatum. All other regions, except hypothalamus, showed a trend in the same direction (RHA/Verh > RLA/Verh). In the hypothalamus, however, [ 3H]imipramine binding for RLA/Verh rats significantly exceeded that found in RHA/Verh animals.

Using the triple test cross to investigate the genetics of behavior in wild populations. II. Escape-avoidance conditioning inRattus norvegicus

The detailed results of a triple test cross using wild rats crossed to partially inbred sublines of the Roman High and Low Avoidance selection strains clearly indicated considerable amounts of additive genetic variation in the wild population for avoidance performance while there is a general absence of nonadditive variation, with the exception of some dominance variation together with duplicate type epistasis. Where present, directional dominance for this phenotype is toward high performance only for later trials, and the effects of any epistasis reinforce this trend. The overall conformity of these results to the predictions from previous laboratory rat studies suggests no reason to reject the representativeness assumption necessary for arguments from genetic architecture in laboratory populations to adaptive significance in contemporary wild populations.

Spontaneous maze ambulation and Hebb-Williams learning in Roman High-Avoidance and Roman Low-Avoidance rats

Several aspects of the maze performance of Roman High-Avoidance (RHA/Verh) and Roman Low-Avoidance (RLA/Verh) rats were compared, using a complex enclosed “exploratory” maze system and the 12 detour tasks of the Hebb—Williams test. In the “exploratory” maze, the behavior of the two selected rat lines differed considerably, with the RHA/Verh rats showing a higher activity level. In the Hebb—Williams series of 12 detour tasks, the RLA/Verh rats exhibited superior performance (except for Task 12) with a larger learning-related decrease of errors from run to run. The greater suppression of activity within an illuminated open field in the center of the “exploratory” maze and the paniclike behavior of some RLA/Verh rats in the most difficult problem (Task 12) of the Hebb—Williams test suggest, together with other existing evidence, that the RLA/Verh rats are more emotional, especially under stressful conditions. The results are discussed within the context of the reversed performance capabilities of the two selected lines in shock- and nonshock-motivated test situations.

Schedule induced ethanol polydipsia in psychogenetically selected lines of rats

Schedule induced ethanol polydipsia was established in 28 male and female rats of two psychogenetically selected lines bred for extremes in active avoidance performance. These rats were maintained at 80% normal body weight and given 36 consecutive daily 45-min sessions with 3% (w/w) ethanol available. During the acquisition phase, food pellets were delivered intermittently on a FT-1 min schedule. Baseline tests preceded and followed the acquisition phase and involved presentation of 45 food pellets together at the start of a test. Roman High Avoidance (RHA/Verh) rats exhibited greater ethanol intake than Roman Low Avoidance (RLA/Verh) rats and female rats drank more ethanol (adjusted for body weight differences) than male rats during baseline and acquisition phases. Furthermore, baseline ethanol intake increased significantly from the initial block to the final block of sessions following acquisition testing, but remained significantly lower than ethanol intake during the final block of acquisition tests. In a second experiment, naive female rats of the two psychogenetic lines were given baseline tests or sessions with food intermittently delivered on a FT-2 min schedule following a period of free feeding or a 20-hr session 3% ethanol was continuously available. In the initial phase of acquisition, fasted RHA/Verh rats drank more ethanol than RLA/Verh rats. In the second phase, undeprived rats of these two lines did not differ in ethanol intake. In a final acquisition phase, fasted RHA/Verh and RLA/Verh rats did not differ significantly in ethanol consumption. Under both deprivation regimens, baseline ethanol intake increased from the initial to the final baseline test. The ethanol consumption of fasted rats in the final acquisition test was significantly greater than that in the final baseline test. Thus, although pronounced and relatively enduring differences in the schedule induced ethanol intake of these two rat lines were observed under the condition of chronically reduced body weight, this strain difference was relatively weak and observed only in the initial phase of acquisition when 20-hr fasted rats were tested.

Effects of scopolamine, pilocarpine, and oxotremorine on the exploratory behavior of two psychogenetically selected lines of rats in a complex maze.

Rats of two psychogenetically selected lines received pretest IP injections of scopolamine hydrobromide (0.25, 1.0, or 4.0 mg/kg), pilocarpine hydrochloride (3.0, 6.0, or 12.0 mg/kg) or oxotremorine sesquifumarate (0.2, 0.4 or 0.8 mg/kg) and were subsequently placed in a complex enclosed maze of the Dashiell type that included a small, central, illuminated arena. Animals receiving pilocarpine or oxotremorine injections were pretreated with methscopolamine to counter the peripheral actions of these muscarinic cholinergic agonists. Following vehicle injections, Roman High-Avoidance rats (RHA/Verh) were significantly more active, explored more maze sectors, and required less time to activate the initial 24 different photocell units uniformly distributed throughout the maze than Roman Low-Avoidance rats (RLA/Verh). Scopolamine, pilocarpine, and oxotremorine depressed locomotor activity, reduced the explored area, and increased the time required to activate the initial 24 different photocell units within this complex maze for both RHA/Verh and RLA/Verh rats. Although the doses of scopolamine injected were approximately equally effective in both rat lines (except for total maze activity), the RHA/Verh rats exhibited significant alterations in several measures of maze patrolling after treatment with the lowest dose of pilocarpine, whereas the RLA/Verh rats did not. In contrast, most of the RLA/Verh rats exhibited very pronounced tremors following treatment with the highest dose of oxotremorine, but none of the RHA/Verh rats did. These results demonstrate that manipulation of the central cholinergic system with scopolamine, pilocarpine, or oxotremorine, despite their different pharmacological mechanisms, impair maze patrolling. Furthermore, the results suggest that the two psychogenetically bred lines of rats investigated are differentially sensitive to central cholinergic manipulation with the muscarinic receptor agonists pilocarpine and oxotremorine.

Acquisition and extinction of gustatory aversion in two lines of rats selectively bred for differential shuttlebox avoidance performance

Consumption of a palatable saccharin—glucose (SG) solution was compared in Roman High Avoidance (RHA/Verh) and Roman Low Avoidance (RLA/Verh) lines of rats in a taste aversion acquisition and extinction paradigm. Prior to treatment, SG-intake in a 1 -h drinking test by RHA/Verh rats was much greater than that by RLA/Verh rats. Both psychogenetic lines increased SG-intake over a series of exposures when each presentation was followed by saline injection, but decreased SG-intake when each presentation was followed by apomorphine injection. At the end of the acquisition phase, RHA/Verh rats treated with a toxic dose of apomorphine drank 36% less SG than RHA/Verh rats that were injected with saline, whereas RLA/Verh rats treated with apomorphine consumed 54% less SG than RLA/Verh rats injected with saline. Following 16 daily presentations of SG but no injections, extinction of the conditioned gustatory aversion was complete in the RHA/Verh group previously treated with apomorphine, but it remained incomplete in the RLA/Verh rats previously treated with apomorphine. This stronger taste aversion exhibited by RLA/Verh rats is in marked contrast to their extremely inferior performance in a shuttlebox active avoidance task. The basis of the behavioral differences in these two psychogenetically selected lines of rats is discussed.

Emotional correlates of selection for avoidance learning in rats

The Roman high-avoidance (RHA) and low-avoidance (RLA) strains of rats were tested and compared with Maudsley reactive (MR) and non-reactive (MNR) strains to assess the relative contributions of emotionality and conditionability to differences between the two Roman strains. The RHA learned significantly faster in active avoidance, but slightly slower in passive avoidance, significantly faster in acquisition of an active approach task, but slightly slower in extinction of active approach tasks despite extensive adaptation and gentling. The RHA showed more ‘rearing’, more activity in the open field and more variety-seeking. Crossing with MNR showed the RHA less reactive in the open field. Results show RLA equivocal in conditionability, more emotional, and perhaps less active.

Differential hypothalamic self-stimulation behaviour in roman high-avoidance and low-avoidance rats

Monopolar electrodes were implanted bilaterally and symmetrically into a small well defined region of the posterior lateral hypothalamus in 11 rats of the selected strains Roman high-avoidance (RHA/Verh, 6 animals) and Roman low-avoidance (RLA/Verh, 5 animals). Intracranial electrical stimulation (ICS) was used to study possible strain difference with respect to self-stimulation behaviour. Using a shuttle-box, the experimental set-up allowed measurements of the animal's preference, aversion, neutrality or ambivalence towards the stimulus. For both rat strains 10 electrode sites were tested with identical stimulation currents (100–600 μA in increments of 100 μA). Significant differences between the selected strains were found for preference (self-stimulation) and aversion: RLA/Verhrats showed self-stimulation at lower stimulation currents than RHA/Verh-rats. At higher currents, both strains showed similar self-stimulation performance. RLA/Verh-rats escaped more often from ICS yielding self-stimulation at five of the six current levels. It is concluded that, in comparison with the RHA strain, RLA/Verh-rats are more sensitive to aversive effects of lateral hypothalamic stimulation. This seems to be associated with an increased sensitivity to the rewarding effects of such stimulation.

Effects of sex and strain on exploratory locomotion and development of nonreinforced maze patrolling

Continuous recording of locomotion in an enclosed maze with no reinforcement other than that intrinsic to ambulation through the maze provided evidence for a dissociation between the efficiency of patrolling the entire maze and locomotor activity. Patrolling efficiency improved with repeated exposure to a single maze or to two similar maze configurations but not with daily presentation of dissimilar mazes. There were only small strain and sex differences in the development of efficient patrolling, whereas locomotor activity was considerably higher in female Roman high-avoidance (RHA) rats than in female Roman low-avoidance rats and higher in RHA female rats than in RHA male rats.

Durées de veille et de sommeil chez les rats des souches Roman

Wakefulness-sleep patterns of male rats belonging to the Roman strains were studied under two environmental conditions: (1) Over 5 hr (12 a.m.–5 p.m.) and following an adaptation period of 18 hr (Short Adaptation condition, SA); (2) Over 23 hr and following an adaptation period of 168 hr (Long Adaptation condition, LA). Several significant differences appeared in the SA condition. In particular, the total duration of wakefulness was shorter and that of paradoxical sleep, longer in the Roman High Avoidance strain than in the Roman Low Avoidance strain. No significant difference appeared in the LA condition, neither over the whole nycthemeral cycle nor during the 12 a.m.–5 p.m. period. According to these findings, the genetic factors that distinguish the Roman strains seem most likely to concern habituation to a new environment rather than to control specifically the sleep-wakefulness phenomena.

Effect of Strain and Level of Shock on the Behaviour of Rats in PSI Experiments

Rats from five strains were tested for the ability precognitively to avoid three levels of shock. There were clear effects of shock and strain on the number of observed Random Behaviour Trials, with the Roman High Avoidance strain being the only one to maintain high levels of Random Behavior Trials at high levels of shock. However, there was no evidence for any psi ability in this experiment and this null result was not affected by either the strain of rat tested or the level of shock delivered. There was no interaction among these factors.

Effects of intertrial crossing punishment and d-amphetamine sulfate on avoidance and activity in four selectively bred rat strains

The effects of punishing intertrial crossing (ITC) were investigated on avoidance response and shuttlebox activity in four selectively bred strains of rats, with and without d-amphetamine sulfate. In the Maudsley nonreactive strain (MNR/Har/Lu), the ITC punishment suppressed the avoidance response significantly, under both drug and nondrug conditions, but no such effects were found in the Maudsley reactive (MR/Har/Lu) and the Roman high-avoidance (RHA/Lu) strains. However, d-amphetamine sulfate facilitated avoidance response in the MR/Har/Lu strain and suppressed it in the RHA/Lu. In the Roman low-avoidance strain (RLA/Lu), d-amphetamine sulfate facilitated avoidance responding and activity, but in the ITC permissible group only.

Water-escape in weanling rats: A link between behaviour and biological fitness

Relationships between behaviour, measured in many standard laboratory settings, and biological fitness are often obscure. By making inferences from the genetic architecture revealed in psychogenetic studies, links between behaviour and biological fitness can be forged. To support these inferences, information is needed about the genetic architecture underlying behaviour which has unequivocal links to fitness. In this study, water-escape in rats is related a priori to fitness. Weanling rats from the Roman High Avoidance and Roman Low Avoidance strains and their reciprocal F 1 crosses are tested in a water-escape apparatus. A strong directional dominance found for rapid escape is in keeping with the assumptions made and confirms the test as a useful tool for psychogenetic studies of rats.