Philippe Ropartz

Effects of isolation, handling and novelty on the pituitary-adrenal response in the mouse

Male Swiss strain mice were individually- or group-housed for four weeks. Basal corticosterone levels did not differ with the type of housing, providing no support for the suggestion that the condition of the individually-housed mouse is stressful. Plasma corticosterone levels also were determined for mice which had been either left undisturbed or exposed to new cages which differed from their home cages by varying degrees. There were elevations in mean plasma corticosterone levels corresponding to the degree of difference between the home cage and the new cage. This finding supports the suggestion that changes in 11-OHCS levels are sensitive measures of environmental changes. Mice forced to remain in novel places exhibited higher plasma corticoid concentrations than animals which were given the opportunity to move freely between familiar and novel places. Corticoid values, as well as neurophysiological and behavioral responses, suggested that the stress induced by forced exploration might be due to the fact that animals are prevented from freely regulating their exposure to novel places rather than to novelty per se.

Effects of methamphetamine on novelty-seeking behaviour by mice

The effects of several doses from 0.125–3 mg/kg of methamphetamine on the novelty-seeking behaviour of male Swiss albino mice were studied. Methamphetamine induced a dose-dependent inhibition of novelty preference. Furthermore, a dose of methamphetamine (1 mg/kg) which strongly decreased novelty preference in naive mice induced a significantly lower decrease in exploration of subjects previously exposed to novelty. These data provide some support for Berlynes (1967) suggestion that amphetamine has a disruptive effect on exploration by producing over-arousal.

Effects of lateral amygdala lesions on the responses to novelty in mice.

Bilateral electrolytic lesions restricted to the lateral, basolateral and basomedial amygdaloid nuclei in mice produced a lack of avoidance responses towards novel stimuli. While controls showed avoidance and burying reactions to a novel object introduced into their familiar environment, lesioned mice displayed a high number of approach responses and a low level of burying reactions. Furthermore, when given the opportunity to move around freely in simultaneously presented novel and familiar places, control mice at first exhibited avoidance reactions to the novel environment before showing novelty preference. There were no avoidance reactions in lesioned mice. These data are consistent with the hypothesis that amygdala plays a specific role in the regulation of defensive reactions.

Responses to novelty and changes in behavior across a 3-week postoperative period in hippocampal-lesioned mice.

Abstract When mice were exposed to novelty, they displayed approach responses towards a novel environment (novelty preference) and avoidance and burying reactions (new object reactions) towards a novel object placed in the familiar environment. Bilateral hippocampal lesions appeared to impair these responses. Lesions significantly reduced new object reactions by increasing the number of approach responses and reducing burying, and impaired preference for novel environment. Furthermore, hippocampal lesions increased eating and self-grooming behaviors. These findings were interpreted as indicating that the hippocampus plays a crucial functional role in the motivational and cognitive processes controling the responses to novelty. Furthermore, lesioned mice progressively recovered most of the normal responses to novelty across a 3-week postoperative period.

Aversive effects and retention impairment induced by acetoxycycloheximide in an instrumental task

AXM, when subcutaneously injected during the first 3 min following the acquisition of a nondiscriminative instrumental learning task, induced an aversion for the food reinforcement which had been associated with the training situation and with the pharmacological treatment. The high number of nonreinforced responses preceding the first reinforced response(RR) that animals performed when tested 6 days after AXM treatment, was not due to forgetting of the lever significance, but to this aversion. Animals treated with AXM showed low levels of lever pressing response and long latencies for their first RR; this deficit did not seem only to be due to food reinforcement aversion; it disappeared, as well as food aversion, when food reinforcement which had been associated with the learning situation and to treatment, was added to the daily feeding regimen during treatment-test interval. It has been shown, moreover, that more than 90 percent of cerebral protein synthesis was inhibited during the 5 hr following subcutaneous AXM injection. These findings are interpreted as an indication that AXM does not affect memory consolidation of a non discriminative instrumental learning.

Pituitary grafts and behavior in mice. Effects of sex of donor and number of pituitary grafts on exploratory and learning abilities

The effects of ectopic pituitary grafts, sex of pituitary donor, and number of isografts (one or two) were examined in intact phenotypically normal male mice of the Snell dwarf strain, using a battery of tests designed to assess exploration and learning-related behavioral processes. Results show that neither sex of pituitary donor nor number of grafts affected behavioral responses to pituitary grafts. Ectopic pituitary grafts increased the level of exploratory activities assessed in a novelty preference test and in the hole board test, facilitated the retention of a step-through type passive avoidance task--contrasting with results in rats--but did not affect spatial orientation in a spontaneous alternation and a water escape task. The results argue for a global effect of the graft, inducing increased emotional reactivity.

Recovery of exploratory capacity after ectopic pituitary homografts in snell dwarf mice (dw/dw)

The effects of ectopic pituitary homografts on free behavior were studied over a period of one month in adult Snell Dwarf mice. Because of anterohypophyseal deficiency, these animals exhibit dwarfism, sterility, and marked behavioral deficits. Beginning on the 16th day after surgery, in addition to a considerable weight gain, grafts result in the total disappearance of inactivity with passive social contact--the behavior most frequently observed in the mutants--to be replaced only by exploration--the most frequently observed behavior in controls. The treatment totally restores the latter behavior. Specific hormonal treatments and biochemical manipulations at different stages would enable identification of the hypophyseal hormones and/or the growth factors involved in the behavioral and morphological changes.

Effect of age at the time of pituitary grafting on behavioral recovery in dwarf mice

The effects of ectopic pituitary isograft implanted in 13- or 21-day-old Snell dwarf mice on their freely expressed behavior were examined over a 14- or 31-day period. This mutant strain has severe anterohypophyseal deficiency which causes high levels of inactivity and abnormally low exploratory activity. The graft totally normalized these behaviors. Results showed that the time necessary for inducing behavioral changes is independent of age of the animals at the time of grafting, but the age at which implantation occurs influences the speed of full behavioral normalization. The possible involvement of prolactin and growth hormone in such behavioral improvement is discussed.

Prolactin similar to ectopic pituitary isograft restores responsiveness in Snell dwarf mice.

THE effects of ovine prolactin (PRL) (2 ± 5 IU a day) and an ectopic pituitary isograft on the responsiveness were examined using locomotor and exploratory activities as measures in PRL-growth-hormone-thyrotropin-deficient Snell dwarf mice (dw/dw). After 5 weeks of treatment, both PRL and the graft restored the two behavioural measures to normal levels. Results clearly demonstrate the involvement of PRL in global behavioural responsiveness and suggest a possible role for PRL in the changes induced by the graft.

Total recovery of response to novelty after ectopic pituitary isografts in Snell Dwarf mice (dw/dw)

The effects of ectopic pituitary isografts on response to novelty were studied in adult Snell Dwarf mice. Because of anterohypophyseal deficiency, these animals exhibit dwarfism, sterility and marked neurochemical and behavioural deficits. When given the opportunity to move around freely in simultaneously presented novel and familiar environments, grafted dwarf (GRAFT Dw) and sham-grafted control (SHAM C) mice showed a significant novelty preference while sham-grafted dwarf (SHAM Dw) mice exhibited no preference. Both SHAM C and GRAFT Dw mice frequently reared and covered the familiar compartment more quickly than the novel compartment, while SHAM Dw mice reared infrequently and covered the two compartments at equal speed. These data reveal in the mutant a total indifference toward its environment and show a total recovery of neotic behaviour after grafting. The literature is very vague concerning the hormonal changes induced after ectopic pituitary grafting but subsequent specific hormonal treatments and biochemical manipulations would facilitate identification of the hypophyseal hormones and/or the growth factors involved in the behavioural changes.