A single administration of interleukin-1 or amphetamine induces long-lasting increases in evoked noradrenaline release in the hypothalamus and sensitization of ACTH and corticosterone responses in rats.

Single administration of the cytokine interleukin-1beta (IL-1) or the psychostimulant amphetamine causes long-term sensitization of the hypothalamus pituitary adrenal (HPA) axis, i.e. enhanced adrenocorticotropine hormone (ACTH) and corticosterone responses weeks later. HPA responses to these stimuli involve activation of hypothalamic corticotropin-releasing hormone (CRH) neurons by noradrenergic projections to the paraventricular nucleus (PVN). In search of the underlying mechanisms, we studied the temporal pattern of HPA sensitization in relation to (1) the reactivity of noradrenergic projections to the PVN and (2) altered secretagogue production in hypothalamic CRH neurons. Single exposure to IL-1 or amphetamine induced cross-sensitization of ACTH and corticosterone responses 11 and 22 days later, but not after 42 days. Amphetamine-induced HPA sensitization was not accompanied by increased costorage of arginine vasopressin (AVP) in CRH terminals, as found previously after IL-1 pretreatment. The reactivity of noradrenergic terminals was assessed by measuring the electrically evoked release of [3H]-noradrenaline from superfused PVN slices. Single administration of amphetamine and IL-1 induced a long-lasting (up to 22 days) increase (up to 165%) of evoked noradrenaline release. This indicates that single exposure to psychostimulants or to cytokines can induce a long-lasting increase in stimulus-secretion coupling in brainstem noradrenergic neurons that innervate the PVN. This common, long-lasting functional change may underlie, at least in part, IL-1- and amphetamine-induced HPA cross-sensitization. In addition, increased AVP signalling by hypothalamic CRH neurons appears to play a role in IL-1-induced, but not in amphetamine-induced, HPA sensitization.

Attenuation of neophobia and conditioned taste aversion in the rabbit.

The phenomenon of taste neophobia to apple juice does exist in the rabbit. It was found that malic acid was the main stimulus source. Attenuation of taste neophobia was due to neuronal processes which took place between rather than during drinking sessions. Conditioned taste aversion learning took place if apomorphine was injected after apple juice intake.

Environmental and hormonal control of the seasonal egg laying period in field specimens of Lymnaea stagnalis.

A study has been made in field specimens of Lymnaea stagnalis of the relationship between environmental factors (temperature, photoperiod, and food) and spontaneous ovipository activity as well as oviposition evoked by injection of the ovulation hormone (CDCH) during a 1-year cycle. It appeared that spontaneous egg laying started in mid-May and ended in mid-September. It is concluded that it is the quantity of assimilated food that triggers the onset of the egg laying season. Its termination is very likely determined by a synergistic action of environmental factors. It is suggested that these factors control the activities of the CDCH-producing neuro-endocrine caudo-dorsal cells. In winter the snails are completely insensitive to injected CDCH, although many large oocytes are present in the gonad. During 2 months before and after the egg laying season, however, many injected snails respond to CDCH. It is argued that these phenomena are caused by changes in the activities of the endocrine dorsal bodies, which control vitellogenesis and the activities of the female accessory sex organs. The changes in the activities of the dorsal bodies are probably controlled by the synergistic actions of the previously mentioned environmental factors. Oviposition latency (interval between CDCH injection and start of oviposition) is much shorter during the egg laying season than in the nonreproductive period. This must be ascribed to the direct effects of temperature.

Recovery from hypobaric hypoxia in the rabbit.

In rabbits, recovery was studied from hypobaric hypoxia elicited by decompression to 190 mm Hg. In the first experiment a pattern discrimination habit was used. A marked latency appeared after hypoxia, before the rabbits started to respond, but once started no difference was found compared to control circumstances. Repeating this procedure 48 h later resulted in a spontaneous decrease in latency, which remained significantly longer than without hypoxia. In the second experiment rabbits were on a time-restricted daily drinking schedule and the water drinking behaviour was registered. Due to the preceding hypoxia the rate of drinking was much lower compared with the control animals, as was the average total fluid intake. After 48 h the impact of hypoxia was much less. In the third experiment the influences of repeated periods of hypoxia upon the heart rate were studied. Rabbits showed a marked bradycardia during hypoxia which was less severe 48 h later. It was argued that studying recovery from hypoxia is potentially valuable to gain information about the effects of cerebral hypoxia and the autonomic responses that influence the final outcome of hypoxic stress in the intact rabbit.

The effect of temperature on spontaneous, and ovulation hormone-induced female reproduction in Lymnaea stagnalis.

Spontaneous oviposition of the freshwater pulmonate snail Lymnaea stagnalis stopped after transfer from 20 degrees to low temperatures (8 and 4 degrees). This was due to a reduction in the activities of the neurosecretory caudodorsal cells (CDC), which produce the ovulation hormone (CDCH). Oviposition latencies (time interval between CDCH-injection and start of oviposition) increased with decreasing temperature. The ovotestis and the female accessory sex organs of snails placed at 8 degrees became less sensitive, and those at 4 degrees became completely insensitive to injected CDCH. This was probably caused by a reduction in activities of the endocrine dorsal bodies (DB), which control vitellogenesis and the activities of the female accessory sex organs. After a change from 4 to 20 degrees, CDCH injections rapidly became effective in inducing egg mass production, and spontaneous oviposition also restarted quickly, suggesting a rapid increase in DB and CDC activities.

Ovulation hormone, nutritive state, and female reproductive activity in Lymnaea stagnalis.

A study of the relation between nutritive state and female reproductive activity as affected by the ovulation hormone (CDCH) has been made in the freshwater pulmonate snail Lymnaea stagnalis. CDCH is produced by the neuroendocrine caudodorsal cells (CDC) in the cerebral ganglia. Spontaneous oviposition ceased within 6 days of the beginning of a starvation period. This is most probably partially due to a reduction in the CDC activities because (1) quantitative electron microscopy showed a nearly 80% decrease in the number of release phenomena in the CDC-axon terminals in the neurohemal area in the intercerebral commissure, and (2) a bioassay showed a considerable reduction in the amount of CDCH in this area. During starvation the ovotestis and the female accessory sex organs became progressively less sensitive and, after 25 days, were completely insensitive to injected CDCH. This was indicated by a decrease in the responses to CDCH injection and, correspondingly, by a gradual increase in the CDCH thresholds for ovulation and egg formation. It is argued that the insensitivity may be caused by a reduction in the activities of the endocrine dorsal bodies. During refeeding, CDCH injections again become effective in inducing egg mass production, followed by resumption of spontaneous oviposition. This suggests a rapid restoration of DB and CDC activities following refeeding.

Synchronous maturation of the female reproductive system and of the ovulation hormone-producing system in Lymnaea stagnalis.

The intercerebral commissures (COMs) of young snails, which are in the male stage (10-15 mm shell height), contain only small quantities of ovulation hormone (CDCH): 0.6 OIU . COM-1 . g-1 snail (1 ovulation inducing unit = threshold dose for ovulation in adult recipients). During the subsequent period of female maturation the quantities of CDCH increase considerably up to a maximum of 47 OIU . COM-1 . g-1 snail at the onset of oviposition. In snails smaller than ca. 21 mm shell height oviposition cannot be induced by COM extract injections. It is concluded that maturation of the female reproductive system and of the ovulation hormone system occur simultaneously, and that both processes are stimulated by the hormone of the dorsal bodies (endocrine organs located upon the cerebral ganglia).

Specificity of ovulation hormones of some basommatophoran species studied by means of iso- and heterospecific injections.

Isospecific injections of intercerebral commissure (COM) extracts of L. stagnalis, L. palustris, and L. ovata (Lymnaeidae) and of extracts of COM/mediodorsal bodies complexes (COM/DB) of Bulinus truncatus (Bulinidae) and Biomphalaria glabrata (Planorbidae) induced oviposition in a high percentage of the experimental snails. Positive results of heterospecific injections between the first three species indicated a likely structural similarity of the ovulation hormones within the genus Lymnaea. The hormones of Lymnaea, Bulinus, and Biomphalaria, however, appeared to be different (negative results of heterogeneric injections).

A rapid in vivo bioassay of the ovulation hormone of Lymnaea stagnalis.

The neurosecretory caudo-dorsal cells (CDC) of the basommatopora Lymnaea stagnalis produce an ovulation hormone (CDCH), which is released at the periphery of the intercerebral commissure (COM). A rapid in vivo bioassay for CDCH has been established and is based on the dose-dependent relationship between the quantity of injected CDCH (COM-extract) and the number of snails responding with the first stages of the egg-mass production process, as determined 30 min after injection. Three types of scores can be distinguished: (1) no response (very low CDCH doses), (2) ovulation only (O), and (3) ovulation and packaging (O + P). With increasing CDCH doses the number of snails responding with O, O + P, and oviposition increases. It is shown that the O response first increases followed by a decrease, while simultaneously, the P response increases. This is caused by the fact that the packaging latency is dose dependent, i.e., at low doses it is greater than 30 min, whereas at higher doses it is less than 30 min. This agrees with the finding that at low doses the oviposition latencies are longer (ca. 20 min) than at higher doses. The size of the egg mass is not dose dependent. Several factors that influence the responses upon which the bioassay is based have been analyzed, i.e., refractory period, photoperiod, and day-to-day variability of the assay snails. Experiments relating to the development of a bioassay are reported. The half-life of injected CDCH appeared to be 30-40 min.

Effect of the photoperiod on the time schedule of egg mass production in Lymnaea stagnalis, as induced by ovulation hormone injections.

In the pulmonate snail Lymnaea stagnalis the neurosecretory caudo-dorsal cells (CDC) produce an ovulation hormone (CDCH) which is released at the periphery of the cerebral commissure (COM). Time schedules of the successive stages of the egg mass production following CDCH injection (COM extract) were determined at 20 degrees. Ovulation is performed rapidly, within 10 to 20 min. The latencies of the other stages are: egg formation, 20-30 min; egg mass formation, 60-90 min; and oviposition, about 120 min. The duration of oviposition is dependent on the size of the egg mass and varies from 5 to 20 min. At a 16-hr photoperiod all stages start 10 min earlier than at a 12-hr photoperiod. It is suggested that the effect of the photoperiod is achieved by a change of release activities of dorsal bodies and/or of CDC. The possibility that a nervous mechanism is involved in the control of the packaging of the egg cells is discussed.