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5-HT and 5-HIAA levels were investigated in three brain regions of Roman high- and low-avoidance rats, following 10, 30 and 60 min of MAO inhibition (pargyline injection). Higher levels of 5-HT in the cortex at 30 and 60 min, as well as a higher disappearance rate of 5-HIAA in the midbrain/medulla region were exhibited by Roman high-avoidance rats, thus further characterizing the differences previously observed in whole brain 5-HT synthesis between these selected rat lines.

This study was designed to test for a genetic association between the propensity to self-stimulate and the capacity for two-way avoidance learning and to search for hippocampal structural correlates of self-stimulation and avoidance. Forty-eight rats from four lines selectively bred for extremes in lateral hypothalamic self-stimulation were used, the parental stocks being designated LC1 and LC2, and the bidirectionally selected lines LC1-Hi and LC1-Lo and LC2-Hi and LC2-Lo (where Hi or Lo denotes high or low self-stimulation), respectively. Twelve animals per line (all females) were tested for the acquisition of two-way avoidance learning during 50 trials. A subsample (eight per line) of the same rats was subjected to hippocampal morphometry, the variables assessed being the proportions of synaptic fields (visualized by means of Timm's stain) in CA3/CA4 at the midseptotemporal portion of the hippocampus. High self-stimulatiors performed better in the shuttle box and showed a parallel selection effect, consisting of a relative enlargement of stratum oriens. The intra-infrapyramidal mossy fiber (IIP-MF) projection did not respond to selection for self-stimulation but was closely associated with differences in avoidance behavior, with poor performers having more IIP-MF.

The effects of low doses of pentobarbital (PB) were measured on the activity levels, shock-induced fighting and avoidance or escape behavior of paired rats of two psychogenetically-selected lines, in multiple shuttle box sessions, following shock-induced fighting or two-way avoidance training. Each pair served as its own control, by receiving drug injections only every second week. Independent of training conditions, the RLA/Verh pairs showed about 90% freezing behavior and no fighting, whereas all RHA/Verh pairs preferred avoidance or escape behavior to fighting. Although their intertrial (shuttling) responses (ITRs) were reduced at the higher doses of PB used, RHA/Verh rats were still capable of most behavioral responses even at 24 mg/kg, whereas all RLA/Verh rats slept at that dose. On the other hand, the ITRs and avoidance responses of the (less active) RLA/Verh rats were increased by injections of 8 and 16 mg/kg PB. The results, especially those pertaining to freezing behavior and changes in activity levels, were discussed in comparison to other selected rat strains which have shown certain similarities to the Roman lines in regard to “emotionality” and associated neurochemical status.

When Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats were individually housed in plastic cages with sawdust bedding and food-deprived (F-D) for 4–5 days, it was found that F-D RHA/Verh rats had more lesions than their unfasted controls and more lesions than F-D RLA/Verh rats. The lesions were mostly petechial in nature and located in the glandular portion of the stomach. Also, F-D RHA/Verh rats which were housed in the same room as the controls, as well as F-D RHA/Verh rats which were housed in a separate room with a strong food odor present, had more lesions than F-D RHA/Verh rats housed in the same separate room when there was no food odor, and when none of the rats present had access to food. When F-D RHA/Verh and F-D RLA/Verh rats were individually housed in metal cages with grid floors, however, a general increase in lesion scores resulted and differences between the two rat lines disappeared, as did differences among the room conditions. Also, many lesions were of an ulcerative nature and were located in the rumenal portion of the stomach. It was concluded that sensory (in this case olfactory, at least) and genetic factors are capable of playing roles in the induction of stomach lesions in rats, and that the type, extent and location of the lesions can depend upon whether or not the animals have access to sawdust bedding.

The effects of a variety of stressful environmental situations on dopamine metabolism in the prefrontal cortex (as assessed by in vivo voltammetry with carbon fiber electrodes) have been compared in two genetically selected lines of rat (Roman high (RHA/Verh) and low (RLA/Verh) avoidance) which differ drastically in their level of emotionality. Heart rate was continuously monitored in these animals (via chronically implanted subcutaneous electrodes) so as to index the emotional reaction to the stressors. An electrochemical signal corresponding to the oxidation of dihydroxyphenylacetic acid (DOPAC) was recorded in the deeper laminae of the anteromedial prefrontal cortex in both lines of rats. Under normal conditions, this signal was stable for at least 4 h and its amplitude was similar in both lines. Introduction of the animals into an unfamiliar environment (30 min), application of a mild tail pinch (10 min) or of a high-intensity loud noise (30 min) or immobilization (20 min) were all associated with an increase in extracellular cortical DOPAC levels in the hypoemotional RHA/Verh line but not in the hyperemotional RLA/Verh line. Similarly, forced locomotion on a rotarod (40 min) provoked a dramatic increase in the amplitude of the cortical DOPAC oxidation peak in RHA/Verh rats and only a mild increase in this parameter in RLA/Verh rats. In RHA/Verh rats, tolerance to this increase was observed when animals were subjected to forced locomotion every day for 5 days. All of the stressful situations investigated provoked an immediate augmentation of heart rate which resumed gradually after cessation of the stressful stimulus; the magnitude and duration of this increase were much greater in RLA/Verh than in RHA/Verh rats. Moreover, in all stress situations, RLA/Verh but not RHA/Verh rats showed behavioral signs of emotional response e.g. defecation, freezing and self-grooming. It is concluded that the increase in cortical dopamine metabolism induced by stress is not connected to the emotional reaction caused by the aversive nature of the stressor but may rather reflect a heightened attention of the animal or activation of cognitive processes in an attempt to cope with the stressor.

Male rats of two lines of rats psychogenetically selected and bred for extremes in performance in shuttle box avoidance received an acute IP injection of chlordiazepoxide (CDP; 2.5, 5.0, 10.0 mg/kg), imipramine HCl (IMI: 0.33, 1.0, or 3.0 mg/kg), or vehicle. The rats were placed, 35 min after injection, in an enclosed maze with either a simple configuration with an unilluminated central arena or a complex configuration with a brightly illuminated central arena, and spontaneous maze patrolling was evaluated. Total locomotor activity during the 6-min maze test was significantly reduced by 5--10 mg/kg CDP for both RHA/Verh and RLA/Verh lines of rats in both the simple and the complex maze configurations. Treatment with 10 mg/kg CDP reduced the total explored area for both rat lines in both maze configurations. In addition, the maze area explored by RHA/Verh rats was also reduced by 5.0 mg/kg CDP for the simple configuration and by 2.5 and 5.0 mg/kg CDP for the complex configuration. Entry into the unilluminated central field of the simple maze was reduced by 5--10 mg/kg CDP only in RHA/Verh rats. In contrast, 2.5 mg/kg CDP significantly increased entry into the brightly illuminated central arena of the complex maze for the RLA/Verh rats. The doses of IMI used were without effect on the parameters of maze patrolling behavior evaluated, with the single exception that the locomotor activity of RHA/Verh rats tested in the simple maze configuration was decreased by 3.0 mg/kg IMI. The results indicate that, although the effects of CDP were generally similar for total activity and the area explored in the two psychogenetic lines investigated, there was a qualitative difference in its effect on entry into an illuminated arena.

Utilizing an automated, Dashiell-type hexagonal maze, it was demonstrated that RHA rats: 1) were more active, 2) reversed direction more often, 3) entered radial (blind) alleys less often, and 4) displayed shorter latencies than did RLA rats. Direction reversals (U-turns) tended to increase from day to day with the RHA rats, whereas the opposite was true for the RLA rats. Nicotine injections (0.2 mg/kg) increased activity and the number of U-turns, shortened the latencies and lessened the likelihood of entering radial alleys for both strains. The RHA rats were more sensitive to nicotine than were the RLA rats in all of these measurements, which varied, depending upon alley length and structural complexity, among the maze configurations.

The effect of nicotine and total alkaloids extracted from smoke on the avoidance behavior of rats under extinction procedure has been measured in an experiment extended over a period of three months. There was no significant difference between the two substances, with both inhibiting the extinction of avoidance response to approximately the same degree. Significance against the control was achieved with all treatments, the effect being significantly greater with the dose of 0.2 mg/kg than with the two doses of 0.1 or 0.05 mg/kg.

Matched pairs of male and female, Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats were tested for shock-induced fighting, and single rats were tested for comparative sensitivity to footshocks. The main finding was that the RLA/Verh rats showed a total absence of shock-induced fighting or posturing. The females of both selected lines showed lower flinch-, shuffle- and jump-shock thresholds than did the males. Although the RHA/Verh rats had lower shuffle and jump thresholds than did the RLA/Verh rats, there was no significant difference in the initial detection of foot-shocks by either group (flinch threshold), and all 3 levels of threshold values for both were well below the 3 mA shock level used in the shock-induced fighting experiment. It was concluded that the genetically-based response suppression (freezing behavior) seen with RLA/Verh rats under these and all shock-stress conditions played a greater role in the inhibition of shock-induced fighting than did sensitivity to footshocks per se.

The frequency of shock-induced fighting, posturing and “no reaction” (running/ jumping or freezing), after acute SC injections of 0, 0.1, 0.2 and 0.4 mg/kg nicotine, was measured in 38 pairs of male and 12 pairs of female rats. Sensitivity of footshock was also measured, at the same nicotine doses, in males. Nicotine inhibited shock-induced fighting in 32 pairs of high-frequency fighting males in a dose-dependent fashion, with fighting being gradually replaced by posturing at the 0.1 and 0.2 mg/kg doses. There was a significant increase in the “no reaction” category (especially freezing behavior) only at 0.4 mg/kg, indicating that reduced activity may have been partly responsible for the reduction in fighting seen at that dose. None of the doses had a significant effect on sensitivity to footshock. Nicotine had no effect on shock-induced fighting in the six low-frequency fighting male pairs, and affected the female pairs only at the 0.4 mg/kg level, where fighting was also decreased due to an increase in the “no reaction” category. It could be concluded that small doses of nicotine, under favorable conditions, were capable of inhibiting shock-induced fighting in rats without altering shock sensitivity or depressing activity.

This experiment sought to determine whether the behavioral differences between the Roman high-(RHA/Verh) and low-avoidance (RLA/Verh) lines of rats could be related to differences in the number and/or affinity of brain muscarinic cholinergic receptors. The binding of the specific muscarinic antagonist 3H-quinuclidinyl benzilate to crude membrane preparations from the cerebral cortex, hippocampus and striatum was determined. There were no significant differences between the two rat lines for the number of muscarinic binding sites (Bmax) or the apparent dissociation constant (KD) as determined by Scatchard analysis of the saturation isotherms. These data indicate that the behavioral differences between RHA/Verh and RLA/Verh rats cannot be accounted for by differences in the number or affinity of brain muscarinic cholinergic receptors.

The behavior of male rats with chronic end-to-side portacaval shunts or control surgery were evaluated in a complex enclosed maze, an open-field arena, and a swim canal. Subsequently, serotonin and 5-hydroxyindoleacetic acid levels were measured for hypothalamus, striatum, hippocampus, and midbrain-medulla. Chronic portacaval anastomosis did not significantly alter any of the behavioral parameters evaluated in the diverse test situations studied, despite a significant elevation of 5-hydroxyindoleacetic acid levels in all brain regions analyzed and the elevation of serotonin levels in hypothalamus and midbrain-medulla.

The comparative effects of three doses of nicotine (0.075, 0.15 and 0.3 mg/kg) were measured on the shuttlebox behavior of highly trained guinea pigs, using 50-trial sessions and a 15 sec CS-US interval. It was found that nicotine counteracted the characteristic intra-session performance decrement seen with this species and, in addition, that the various doses of nicotine could be differentiated from each other and the control (physiological saline) in this test. These results were obtained through the measurement of response latencies and the recording of intertriai responses which, for the purposes and conditions of this and future studies of this type, were shown to be more effective parameters than the measurement of avoidance frequency alone.

In the present experiments, plasma concentrations of corticosterone, ACTH, prolactin, blood glucose, serum free fatty acids, core temperature and fecal boli were measured immediately following the exposure of Roman high- and low-avoidance rats (RHA/Verh, RLA/Verh) to various stressful situations. As compared to RLA/Verh rats, the RHA/Verh animals showed an attenuated emotional response in “non-self-menacing” (novel environment) situations. Differences between the 2 selected lines were not generally found in unstressed rats or in “high-stress” (ether, immobilisation, footshock) situations.

Male and female rats of two lines psychogenetically selected for bipolar extremes in shuttle box avoidance were evaluated for tremor, salivation, chromodacryorrhea, 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 the chromodacryorrhea response, with femles exhibiting a greater response following oxotremorine than males. In a subsequent experiment using female rats of both rat lines, it was demonstrated that pretreatment 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 chromodacryorrhea 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.

Bei trainierten Meerschweinchen wurde der Prozentsatz von Vermeidungsreaktionen, deren Latenzzeiten, und die Spontanreaktionen zwischen den Reizen in einer «two-way shuttlebox» unter dem Einfluss von Mecamylamin gemessen. Unter Verwendung eines flexiblen Dosierungsplanes wurde fur 1 mg/kg Mecamylamin eine signifikante Depression des «Shuttlebox»-Verhaltens beobachtet. Fur die Verminderung der Vermeidungsleistung innerhalb einer Sitzung, die fur diese Spezies charakteristisch ist, war die gemessene Reaktionslatenz der empfindlichste Indikator.