Effect of centrally administered cholecystokinin on feeding behavior induced by electric stimulation of the lateral hypothalamus in the rabbit

In experiments on 15 freely moving rabbits cholecystokinin octapeptide sulfate (CCK-8-S) in a dose of 10 ng considerably suppressed alimentary behaviour of the animals elicited by electrical stimulation of the lateral hypothalamus. Increasing of the peptide doses to 100 and 200 ng elicited an analogous effect. CCK-8-NS in 10 ng dose produced a lesser effect on feeding of the animal, but increasing of the dose of nonsulphated CCK to 100 ng led to a considerable prolongation of feeding. CCK-8-S and CCK-8-NS in doses used did not affect the reaction of avoidance in rabbits caused by electrical stimulation of the ventromedial nucleus of the hypothalamus.     

Urocortin in the lateral septal area modulates feeding induced by orexin A in the lateral hypothalamus

The intermediate portion of the lateral septum (LSi) contains high levels of urocortin (UCN) peptide and type 2 corticotropin-releasing hormone (CRH) receptor (CRHR2) and has anatomic and functional connections with the lateral hypothalamus (LH). We tested the effect of UCN in the LSi on feeding. Injection of 10 or 30 pmol UCN into LSi significantly decreased feeding in food-deprived rats for 24 h without producing conditioned taste aversion (CTA). Pretreatment with a CRH receptor antagonist, alpha-helical CRH (alpha-hCRH), blocked the inhibitory effect of UCN on deprivation-induced feeding at 1 and 2 h postinjection. Furthermore, UCN in the LSi significantly decreased feeding induced by LH-injected orexin A at 2 and 4 h postinjection, and addition of alpha-hCRH blocked the inhibitory effect of UCN on orexin A-induced feeding. In conclusion, UCN significantly inhibits feeding induced by deprivation and LH-injected orexin A without producing a CTA, an effect that is mediated by CRHR2. These data define the LSi as an important site for UCN-induced anorexia and indicate that LSi UCN may influence orexin A feeding signals in the LH.     

Conjugation of the neuronal impulse activity in the rabbit neocortex during self stimulation of the lateral hypothalamus

Correlation of impulse activity of visual and sensorimotor neurons of both hemispheres in 10-s interval after self-stimulation of the right and left lateral hypothalamus was studied by plotting cross- and autocorrelation histograms. The number of cell pairs, in which sensorimotor neurons discharged after visual ones, increased after self-stimulation (from 24 +/- 6 to 44 +/- 7%). Frequencies of the alpha- and theta-range in crosscorrelograms increased; the alpha frequency increased mainly in the right hemisphere, while the theta frequency increased in the left hemisphere. The interhemispheric asymmetry in the interaction between cortical neurons was not associated with the side of hypothalamic stimulation.     

Somatosensory evoked potentials by tibial nerve stimulation in the rabbit

Somatosensory evoked potentials by tibial nerve stimulation were obtained in ten New Zealand rabbits. The subcortical or cortical source of the three negative and three positive peaks present in the first 55 ms is discussed viewing the results obtained by different surface electrode locations and by stereotaxic recordings. The authors report interanimal, interhemispheric and test-retest variability of latencies and amplitudes of subcortical and cortical components.     

Insatiable feeding evoked in rats by recurrent perfusion of neuropeptide Y in the hypothalamus

Hyperphagic-like intake of food was determined in the unrestrained rat during the sustained elevation over time of neuropeptide Y (NPY) within the paraventricular nucleus (PVN) and surrounding hypothalamic regions. A single guide tube was implanted stereotaxically in each of 22 rats for localized, intermittent perfusions of a CSF vehicle, nondeprotected NPY(1-36) or native NPY. Each site in the PVN of the fully sated rat was perfused repeatedly over a 5.0-h interval by means of a standard push-pull cannula system at a rate of 20 microliters/min for 6.0 min in one of three concentrations: 0.2, 1.0 and 2.0 micrograms/min. Two perfusions of 1.0 micrograms/min NPY evoked an intake of 4.6 +/- 1.1 g of food over a 3.0-h period, whereas 4-7 and 8-15 perfusions of this concentration of NPY, distributed over 5.0 h, induced the sated rats to eat a total of 12.0 +/- 1.1 g and 33.2 +/- 3.0 g, respectively. During a fixed number of 10 hypothalamic perfusions distributed over 5.0 h, concentrations of 0.2 and 2.0 micrograms/min NPY caused a cumulative intake of food in the rats of 14.2 +/- 2.0 g and 31.7 +/- 3.3 g, respectively. Under each condition, parallel push-pull perfusions of either control solution in the same hypothalamic sites were without effect on feeding. During the 5.0-h interval of repeated perfusions, successive bouts of eating occurred with individual intakes of food reaching as high as 49.0 g, which exceeded by up to two-fold the entire daily consumption of food. However, ingestion of water was unaffected by perfusion of NPY.(ABSTRACT TRUNCATED AT 250 WORDS)     

Raised excitability produced in cortical neurons by reinforced stimulation of the lateral hypothalamus

Response was recorded in the pyramidal tract (PT) under three experimental situations modelling the shaping of conditioned reflex (CR) during experiments on unrestrained but unanesthetized rabbits. The first paradigm consisted of direct stimulation of two points on the sensorimotor cortex, the second of the same stimuli combine with electrical stimulation (used as additional reinforcement) of the lateral hypothalamus (LH), and the third of LH stimulation in response to a rise occurring in PT response to above control level (modelling instrumental CR). An overall increase in the monosynaptic wave indicative of altered efficacy of synaptic connections was most commonly observed under all these conditions. Increase in the component directly reflecting pyramidal neuronal excitation appeared significantly more pronounced in the second and third than in the first experimental paradigm. The data obtained would point to reinforced efficacy of excitatory synaptic connections as the principal mechanism of CR, while the changed quality of electrical excitability at the membrane of cortical neurons reflects mechanisms underlying the contribution of reinforcement triggered by LH activation in cortical reordering of the motivational/emotional component of reinforcement.Higher Nervous Activity and Neurophysiology Research Institute, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 21, No. 6, pp. 805–811, November–December, 1989.     

Spatial configuration of rabbit superior collicular evoked response to punctiform afferent stimulation

Evoked potentials arising in the rabbit superior colliculus in response to punctiform stimulation of the receptive field were studied. This response has only negative polarity at the focus of maximal activity and does not exhibit reversal of the potential which is a characteristic feature of the response to diffuse stimulation. The evoked potential was recorded at depths of between 0.1 and 0.9–1.0 mm from the collicular surface, corresponding to the stratum griseum superficiale. The response disappeared when the stimulating spot was shifted through 4–6° away from the optical position. It is suggested that evoked potentials to punctiform stimulation can give more complete information on the location of different synapses.A. N. Severtsov Institute of Evolutionary Morphology and Ecology of Animals, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 11, No. 5, pp. 441–450, September–October, 1979.     

Analysis of the effect of increasing electrodermal stimulation on the somatovegetative reactions evoked by stimulation of the ventromedial hypothalamus

The influence of increasing electrodermal stimulation (EDS) on the dynamics of the somatovegetative reactions evoked by electrical stimulation of negative emotiogenic regions of the hypothalamus was studied. EDS produced a blocking effect on the somatovegetative reactions evoked by stimulation of the ventromedial hypothalamus (VMH). Pretreatment with naloxone prevented the effects of EDS. Injection of beta-endorphine in a dose of 10 micrograms to the lateral ventricules of the animal brain also blocked the somatovegetative reactions during VMH stimulation. Injection of beta-endorphine in doses of 50-100 micrograms enhanced and prolonged the somatovegetative reactions evoked by VMH stimulation. Elevated arterial blood pressure, pronounced bradycardia, extrasystoles, muscle tremor, and pathologic respiration were recorded. These disorders were completely reversed by EDS. It is assumed that both opiate peptides and their receptors are involved in the mechanism of the somatovegetative reactions evoked by VMH stimulation, experiencing the influence of EDS.     

Substance P degrading systems of rat parotid and hypothalamus

Inactivation of substance P and its C-terminal hexapeptide analog [p-Glu⁶]substance P6–11 was studied in rat parotid and hypothalamic slices. It was found that in the parotid slice system the decay of substance P induced K⁺ release occurs concurrently with a decrease in the biologically active concentration of the peptide in the medium. The inactivation was further studied using [p-Glu⁶]substance P6–11 as substrate in the parotid and in the hypothalamic slice systems. In both tissue preparations the hexapeptide is degraded to small peptide fragments by metalloendopeptidase. Separation of the peptide fragments by high performance liquid chromatography and determination of their amino acid composition showed that in the hypothalamic slice system the major cleavage of the hexapeptide analog occurs between Phe⁸-Gly⁹ with minor cleavage sites between Phe⁷-Phe⁸ and Gly⁹-Leu¹⁰. In the rat parotid slice system the major cleavage occurs between Gly⁹-Leu¹⁰ with a minor cleavage site between Phe⁷-Phe⁸. The degradation of the hexapeptide analog in the hypothalamic system was inhibited 77% and 67% by treatment with 1 mM p-chloromercuriphenylsulfonate and p-chloromercuribenzoate, respectively, whereas in the parotid system these reagents inhibited the degradation of the hexapeptide only by 15% and 8%. These results may indicate that different proteases in the parotid and hypothalamus are involved in degradation of substance P. Kinetic studies, including the use of various inhibitors as well as competition by the peptide hormones somatostatin, LHRH, TRH and Leu-enkephalin-NH₂, revealed that in both tissues the hexapeptide analog is a preferred substrate for degradation by protease of considerable specificity towards the C-terminal sequence of substance P. It is suggested that this metalloendopeptidase may be important in the termination of the substance P response.     

Substance P in the central mechanisms of the escape reaction

The role of substance P in the central mechanisms of escape reaction elicited by electrical stimulation of the ventromedial hypothalamus was investigated in chronic experiments on rabbits. Intravenous injection of substance P (30 micrograms/kg) led to a short-term (less than 10 min) increase in the threshold of stimulation of the ventromedial hypothalamus and to more stable (up to 1.5 h) disorders of the hippocampal-hypothalamic relations. After substance P injection the inhibitory effects of the dorsal hippocampus but not the facilitating influences of the midbrain reticular formation on excitability of the hypothalamic motivation center were found to be lacking. Disorders of the central mechanisms of escape reaction after substance P injection correlated with new patterns of the main EEG rhythms in different areas of the brain cortex in response to the ascending excitations of the limbic-midbrain structures. Interpreting the mechanisms of substance P involvement in escape reaction the authors point to the ability of the given peptide to interact with different transmitter systems of the brain and opiate receptors and to alter the brain blood circulation.     

Modulation of pyramidal response in the rat sensorimotor cortex after combined stimulation of the lateral hypothalamus and the sensorimotor cortex

It was shown during experiments on unrestrained rats that rhythmic stimulation of the pyramidal tract produced a statistically significant increase in the functional activity of neuronal populations of the sensorimotor cortex, manifesting as potentiation of the primary, positive phase of pyramidal cortical response. Combined rhythmically matched stimulation of the pyramidal tract and of the lateral hypothalamus leads to statistically significant enhancement in potentiation of the positive phase of pyramidal cortical response compared with effects produced independently of hypothalamic involvement. When stimulation of the pyramidal tract and the lateral hypothalamus are combined with stimulation applied at the same periodicity to the sensorimotor cortex, a further statistically significant enhancement in potentiation of the positive phase of pyramidal cortical response is seen in addition to the potentiating effect produced by hypothalamic stimulation.Institute for Brain Research of the All-Union Scientific Center of Mental Health, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 18, No. 3, pp. 367–373, May–June, 1986.     

Substance P: Regional distribution and specific binding to synaptic membranes in rabbit central nervous system

Regional distribution of endogenous substance P and the specific [³H]substance P binding to synaptic membranes in rabbit central nervous system were investigated. The highest level of substance P was found in mesencephalon, followed by diencephalon, corpus striatum, hippocampus, pons-medulla and cortex. In spinal cord, much higher amount of substance P existed in dorsal half than in ventral half. Most of the substance P present in the areas enriched in substance P was located in crude mitochondrial P₂ fractions containing nerve endings. A saturable, high affinity, specific binding of [³H]substance P in synaptic membranes was found. The apparent maximal number of binding sites was 95.7 fmole/mg protein, while the dissociation constant (K_D) was 2.74 nM. The binding was displaced by substance P sequence fragments and the related peptides with relative potencies generally parallelizing their pharmacological activities. The distribution of such specific binding generally correlated with endogenous substance P. The presence of such binding sites for substance P in synaptic membranes suggests a possible role for substance P as a transmitter or modulator of neural function.     

Orexin-induced feeding requires NMDA receptor activation in the perifornical region of the lateral hypothalamus

Food intake is stimulated following administration of orexin-A into the perifornical region of the lateral hypothalamus (LH/PFA). Orexin neurons originating in the LH/PFA interact with a number of hypothalamic systems known to influence food intake, including glutamatergic neurons. Glutamatergic systems in the LH/PFA were demonstrated to initiate feeding through N-methyl-d-aspartic acid (NMDA) receptors. Male Sprague-Dawley rats fitted with brain guide cannulas to the LH/PFA were used in two experiments. In the first experiment, a combination microdialysis/microinjection probe was used to deliver artificial cerebrospinal fluid (aCSF) or 500 pmol of orexin-A into the LH/PFA. Orexin-A increased interstitial glutamate to 143 +/- 12% of baseline (P < 0.05), which remained elevated over the 120-min collection period. In the second experiment, the NMDA receptor antagonist d-2-amino-5-phosphonopentanoic acid (d-AP5; 10 nmol) was administered before orexin-A. The orexin-induced increase in food intake (from 1.1 +/- 0.4 to 3.2 +/- 0.5 g, P < 0.05) during the first hour was absent in rats receiving d-AP5 + orexin-A (1.2 +/- 0.5 g). There was no effect of d-AP5 alone on food intake. These data support glutamatergic systems in the LH/PFA mediating the feeding response to orexin-A through NMDA receptors.