Effects of ICV administration of neurotensin and analogs on EEG in rats

The electroencephalographic (EEG) effects of the ICV administration of neurotensin (NT 1-13), NT 1-8 (an inactive neurotensin fragment) and D TYR-11 NT (a long-lasting analog of neurotensin) were studied in rats. In awake rats, NT 1-13 (30 micrograms) and D TYR-11 NT (10 micrograms) induced an increase of the power spectrum in the theta range activity (4-7 Hz). In rats recorded during the sleep-wakefulness cycles, NT 1-13 (10 and 30 micrograms) and D TYR-11 NT (10 micrograms) had an awakening effect and also induced an increase of latency to the first episode of the different sleep stages (intermediate stage and slow wave sleep). NT 1-8 (30 and 90 micrograms in awake rats, 10 and 90 micrograms for sleep-wakefulness cycles) was inactive in all these experiments. Thus, it seems that all these effects can be linked to neurotensin receptors; indeed only fragments which recognize receptors possess an EEG activity.     

Effect of intracerebral administration of NMDA and AMPA on dopamine and glutamate release in the ventral pallidum and on motor behavior

The present study investigates the modulation of the ventral tegmental area (VTA)-ventral pallidum (VP) dopaminergic system by glutamate agonists in rats. The glutamate receptor agonists N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were infused via reversed microdialysis into the VTA, and dopamine (DA), glutamate, and aspartate levels in the VTA and ipsilateral VP were monitored together with motor behavior screened in an open field. NMDA (750 microM) infusion, as well as AMPA (50 microM) infusion, induced an increase of DA and glutamate levels in the VTA, followed by an increase of DA levels in the ipsilateral VP and by enhanced locomotor activity. The increase of DA in the VP was similar after administration of these two glutamate agonists, although motor activity was more pronounced and showed an earlier onset after NMDA infusion. Glutamate levels in the VP were not increased by the stimulation of DA release. It is concluded that DA is released from mesencephalic DA neurons projecting to the VP and that these neurons are controlled by glutamatergic systems, via NMDA and AMPA receptors. Thus, DA in the VP has to be considered as a substantial modulator. Dysregulation of the mesopallidal DA neurons, as well as their glutamatergic control, may play an additional or distinct role in disorders like schizophrenia and drug addiction.     

Effects of systemic and intracerebral administration of glucose oxidase on the blood sugar level in rats.

Intravenous administration of 10 to 40 U/g b.w. glucose oxidase produced hypoglycaemia in a dose-dependent manner. The enzyme-induced drop of the blood sugar level was associated with significant rise in serum potassium and the concentration of free fatty acids. Intracerebral application of glucose oxidase through chronically implanted cannula into the ventromedial, lateral hypothalamus, preoptic region and amygdaloid complex of nuclei failed to change the blood sugar level, although a moderate increase of the free fatty acids and corticosterone concentrations occurred. The local application of enzyme in the locus coeruleus region led to a significant rise of the blood sugar concentration. The observations suggest the sensitivity of brainstem catecholaminergic neuronal system to hypoglycaemia.     

Differential effects of aging on EEG after baclofen administration

Baclofen is a selective gamma-aminobutyric acid (GABA) type B agonist that may have important medicinal uses, such as in analgesics and drug addiction treatment. In addition, evidence is accumulating that suggests GABAergic-mediated neurotransmission is altered during aging. This study investigated whether baclofen administration (5 mg kg⁻¹) induces differential effects on cortical electrical activity with age. Electroencephalograms (EEGs) were recorded from young (3–4 months) and aged (15–17 months) rats, and both the absolute and relative powers in five frequency bands (delta: 2–4 Hz; theta: 4–8 Hz; alpha: 8–12 Hz; beta: 12–20 Hz; gamma: 20–100 Hz) were analyzed. Before administration of baclofen, we found that the EEG relative power in the beta band was higher in the aged than that in the young rats. After administration of baclofen, there was a slower increase in the relative power in the delta band in the aged than that in the young rats. Moreover, there was no significant difference between the two age groups in absolute power in any frequency band. These findings indicate that baclofen treatment appears to differentially modify cortical EEG activity as a function of age. Our data further elucidate the relationship between GABA_B receptor-mediated neurotransmission and aging.     

Effects of intranasal administration of 5-hydroxytryptamine-modulin endogenous serotonergic modulator on rat behavior

This article presents the study of the effects of 5-hydroxytryptamine-modulin??a poorly studied endogenous peptide (Leu-Ser-Ala-Leu)??which specifically interacts with 5-HT1_B-auto- and heteroreceptors. Data obtained in the experiments on rats suggest prolonged anxiolytic and antidepressive effect of intranasal 5-HT-modulin administration and give evidence to an essential role of endogenous 5-HT-modulin in the regulation of anxiety and depression.     

Effects of intracerebroventricular administration of a caspase-3 inhibitor Z-DEVD-FMK on behavior of rats

Rats received intracerebroventricular injections of z-DEVD-FMK (caspase-3 inhibitor) or z-FA-FMK (control peptide) in a dose of 3 nmol. Administration of z-DEVD-FMK significantly decreased the number of avoidance reactions in some blocks of trials in active avoidance (shuttle box) learning. However, only slight effect of the caspase inhibitor across the session was found. Z-DEVD-FMK impaired development of some essential components of the two-way active avoidance performance, such as escape reaction, conditioned fear reaction, and inter-trial crossings. Z-DEVD-FMK did not impair working memory in the spontaneous alternation behavior paradigm. Z-DEVD-FMK affected neither emotionality nor locomotor activity in the open-field test. It also did not influence behavior in the light-dark chamber. Measurement of caspase-3 activity in rat brain regions involved in active avoidance learning revealed z-DEVD-FMK-related inhibition of the enzyme activity most pronounced (about 30%) in the fronto-parietal cortex; a similar effect was close to significant in the hippocampus. The results suggest the involvement of brain caspase-3 in selected forms of learning.     

Effects of acute and chronic administration of Cannabis sative extract on the mouse-killing behavior of rats

The muricidal behavior of spontaneous killer rats was blocked after the first injections of an extract of $\text{Cannabis sativa}$ corresponding to 8.8 mg of Δ9-tetrahydrocannabinol. On the contrary, to rats which did not show this behavior spontaneously, the chronic administration of the extract induced mouse-killing behavior; this effect of marihuana was potentiated by starvation which, by itself, did not interfere with the behavior of the non-killer rats. These results tend to support the view that cannabis has a dual action. Suppression of muricidal behavior may occur due to the acute depressant effects of marihuana. Under chronic administration, however, tolerance develops to these effects unmasking hyperemotionality and/or irritability which may induce killing behavior in previously non-killer rats.     

Conditioned taste aversion elicited by intracerebral administration of drugs

Conditioned taste aversion (CTA) is a vital adaptive reaction governed by highly reliable but poorly understood central mechanisms. In an attempt to elucidate the site of action of various CTA eliciting drugs, equipotent dosages were applied by the systemic (i.p.) and intracerebral (i.c.) route. Rats were offered water on days 1 and 2. On day 3 they received 0.1% sodium saccharin (CS) followed by pentobarbital anaesthesia and i.p. or i.c. injection of the drug (US). After water on day 4, the rats were allowed to choose between water and saccharin on day 5. The putative central action of amphetamine was not confirmed by this experimental arrangement, since CTA was evoked by only moderately (about 10 times) lower i.c. than i.p. dosages. Similar ratio of the i.c. to i.p. effective dosages was obtained with carbachol. On the other hand, CTA of clearly central origin was caused by harmaline and by other monoamine oxidase inhibitors, pargyline and clorgyline, which elicited comparable aversion using 500, 400 and 250 times lower i.c. than i.p. dosages, respectively. The intracerebral gradient of the effect pointed to the lower medulla (inferior olive, raphe nuclei) as the critical brain region and to serotonin as the transmitter participating in the aversive labeling of the gustatory stimulus. The CTA-forming mechanism can also be studied by analysing the action of drugs, e.g. convulsants, which do not produce CTA even when applied at highly toxic dosages (LD 50) eliciting long lasting convulsions (picrotoxin, 5 mg/kg; bicuculline, 5 mg/kg). It is concluded that comparison of brain events elicited by drugs which can or cannot serve as unconditioned stimuli in the CTA paradigm may substantially contribute to the exploration of the underlying neural mechanisms.     

Effects of acute and chronic administration of exorphin C on behavior and learning in white rat pups

We studied the behavior of 21- and 35-day-old white rat pups in the “open field” and the learning of 36- to 41-day-old pups in a maze with food reinforcement. An opioid fragment of wheat gluten exorphin C (YPISL) was injected to pups chronically from day 1 to day 14 of their life or immediately prior to testing. We found that an acute peptide injection did not change animal behavior. The chronic intraperitoneal administration of the peptide at the same dose of 5 mg/kg significantly increased exploratory activity, decreased anxiety, and improved learning. Delayed exorphin C effects were more expressed in female rats.     

Effects of intracerebral administration of IL-1beta on reactive behaviors of astrocytes and macrophages in the injured brain of newborn rats

Newborn male rats were subjected to a mechanical lesion of the left cerebral hemisphere. Thereafter, a single dose 5 or 500 units (U) of recombinant rat interleukin-1beta (IL-1beta) was injected into the lesion cavity. One or 2 days after the injury, the rats were injected with 3H-thymidine to label dividing cells. Brain sections were subjected to GFAP immunocytochemistry or BSI-B4 lectin histochemistry to visualise astrocytes or macrophages, respectively. Autoradiography was used to detect cells proliferating within the region of injury in the immunocytochemically stained brain sections. The strongest mitogenic effect of IL-1beta on astrocytes (labeling index) was observed on day 1 after injury while a dose-dependent increase in their GFAP-immunoreactivity occurred on day 2. At 500U dose, IL-1beta significantly reduced infiltration of macrophages on posttraumatic days 1 and 2 but did not influence their proliferation. Thus, effects of IL-1beta on the occurrence of macrophages were opposite to those on the GFAP-immunoreactivity of astrocytes and their proliferation. It appears to suggest existence of different mechanisms controlling reactive behaviors of the two cell populations.     

Effects of thermal pain stimulus on EEG

Experiments were carried out on conscious rabbits with electrodes chronically implanted into sensorimotor cortex (MSC), ventro-postero-lateral thalamic nuclei (NVPL), periaqueductal grey matter (PAG) and midbrain reticular formation (MRF). Thermal pain stimulus (52 degrees C) lasted 10 s and was applied to the forepaw of the animal. Analysis of bioelectrical activity (20 sec periods) before and after the stimulation was performed by means of automatic methods using the algorithm of Fast Fourier Transform (FFT). It was found that pain stimulation resulted in a characteristic response in every studied structure and that this response was blocked by morphine.     

Analgesic activity of enkephalins following intracerebral administration in the rat

Methionine- and leucine-enkephalin were found to be potent, short-acting analgesics in the tail flick test in rats following intracerebral administration, via chronically indwelling cannulae, into the midbrain periaqueductal gray. Morphine sulfate was approximately 4 times as potent as the enkephalins when infused into this same brain site. The analgesia produced by the enkephalins and by morphine was inhibited by pretreatment with naloxone.     

Analgesic activity of substance P following intracerebral administration in rats

Substance P was found to be a potent, long-lasting analgesic in the tail flick test in rats following intracerebral administration, via chronically indwelling cannulae, into the midbrain periaqueductal gray. Substance P was approximately five times as potent as morphine sulfate on a weight basis; however, it was 25 times more potent than morphine on a molar basis. The analgesic activity produced by Substance P was significantly antagonized by pretreatment with naloxone, a narcotic antagonist. The analgesic activity of Substance P exhibited a rapid onset (1 min.), peaked by 3 minutes post infusion and its duration of activity was between 30 and 60 minutes. Thus, Substance P may be yet another endogenous analgesic peptide.     

Effects of peripheral administration of recombinant human interleukin-1 beta on feeding behavior of the rat

This study was undertaken to investigate the changes in feeding behavior, including ambulatory activity, induced by a single injection of Interleukin-1 beta (IL-1) (2 micrograms/rat) at 18:00, just before the dark phase. For this purpose, we used the Gunma University-type automatic apparatus for continuous and direct measurement of ambulation and drinking. A significant decrease in food intake was observed for 12 hours after treatment with IL-1. Peripheral administration of IL-1 also produced a marked decrease in ambulatory activity within 3 hours which continued for 6 hours. In addition, IL-1 produced a marked decrease in drinking behavior during the first 6 hours. We reported here the changes in consummatory and ambulatory behavior of rats after acute administration of IL-1. The sickness which IL-1 produced may, at least in part, contribute to these phenomena, although precise mechanisms are still unknown.