Heat-escape behavior in the rat following intrahypothalamic injection of acetylcholine

The effects of preoptic/anterior hypothalamic injections of acetylcholine on heat-excape behavior and hypothalamic temperature were investigated in unrestrained rats implanted with bilateral cannulae. Two types of responses were observed, either a fall in hypothalamic temperature coupled with an increase in behavioral responses to escape heat or a rise in hypothalamic temperature associated with little or no change in behavioral heat-escape responses. The fall in hypothalamic temperature observed in one group of rats was significant and was associated with a dose-dependent increase in heat-escape responding. The rise in hypothalamic temperature noted in the other group of rats was nonsignificant, and the associated behavioral responses were variable. Distinct anatomical differences in cannulae loci between the 2 groups were not apparent. It is concluded that acetylcholine activates the heat-dissipating control system of the rat hypothalamus and that the hyperthermic effects of acetylcholine are nonspecific.     

Behavioral suppression using intracranial reward and punishment: effects of benzodiazepines

Rats were chronically implanted with electrodes aimed at the lateral hypothalamus (LH) and the dorsal central gray (DCG) and trained to press a lever that delivered rewarding stimulation of the LH and punishing stimulation of the DCG. In this situation, both diazepam (5-20 mg/kg, PO) and bromazepam (2-10 mg/kg, PO) caused a marked dose-dependent increase of the lever pressing response in the punished period. In addition, the facilitation of lever pressing in unpunished period was also seen in diazepam (5 and 10 mg/kg). These results show that behavioral suppression on lever pressing maintained self-stimulation reward is inducible following DCG stimulation, and that benzodiazepines exhibit an anti-behavioral suppression effect in this situation.     

Limbic connections to the lateral preoptic area: a horseradish peroxidase study in the rat

Horseradish peroxidase, 13% Sigma Type VI, was administered iontophoretically to the lateral preoptic area (LPA) of male hooded rats. Animals were perfused intracardially on the following day and brains were removed and sliced in the coronal plane into 50 microns sections. Alternate sections were processed with DAB and BDH for the brown and blue reaction products and later examined by bright and dark field microscopy for the presence and location of retrogradely labeled neurons. Results indicate that there are a significant number of limbic efferent connections to the LPA. Afferents to the LPA originate in the prefrontal corex, nucleus accumbens, diagonal band and olfactory structures, lateral and medial septum, stria hypothalamic tract and stria terminalis, the magnocellular and medial preoptic nuclei, along the extent of the medial forebrain bundle in the LPA and LH, anterior and basolateral amygdala, ventromedial caudate-putamen, stria medullaris and lateral habenula, the stellatocellular-periventricular, ventromedial, arcuate and anterior hypothalamic nuclei, the perifornical area, zona incerta, ventral medial thalamic area, ventral tegmental area of Tsai, interpeduncular nucleus, reticular zone of the substantia nigra, mesencephalic periaqueductal gray and reticular formation, all aspects of the raphe nuclei and the locus coeruleus. Results are discussed in terms of known anatomical and neurophysiological data and the similar limbic inputs observed for lateral hypothalamic neurons which are found along the extent of the medial forebrain bundle.     

Hypothalamic Pituitary Function Testing on Children Receiving Carbamazepine or Sodium Valproate

An investigation of hypothalamic pituitary axis (HPA) function was performed on children and adolescents receiving long-term monotherapy with either carbamazepine (CBZ) or sodium valproate (NaV). There was a significant reduction in total T4 in the CBZ group. Free T4, T3, and thyroid-stimulating hormone response to thyrotropin-releasing hormone were similar in both groups. All patients produced an adequate growth hormone response to either arginine or L-Dopa. Basal cortisol levels were similar in both groups. An appropriately increased response in luteinising hormone, prolactin, testosterone, and oestradiol occurred in those after puberty. The results suggest that HPA function in children is not compromised by long-term monotherapy with CBZ or NaV.     

Further evidence for hypothalamic asymmetry in endocrine control of the ovary

Nance D.M., M. Bhargava and G.A. Myatt. Further evidence for hypothalamic asymmetry in endocrine control of the ovary. BRAIN RES BULL 13(5) 651–655, 1984.—The differential release of FSH and LH associated with hemigonadectomy (hemi-x) of prepubertal male rats can be blocked by unilateral hypothalamic deafferentation located on the side ipsilateral, but not contralateral, to the hemi-x. Also, ovarian compensatory hypertrophy (OCH) in prepubertal female rats can be blocked by ipsilateral, but not contralateral, hypothalamic hemi-islands. Both these endocrine phenomenon are limited to knife cuts on a particular side of the brain. These results suggest that there are neural connections with the gonads which are involved in endocrine regulation and that hypothalamic control of the endocrine system may be asymmetrically organized. In support of this, the present study shows that in adult female rats, unilateral injections of the excitotoxin kainic acid (1.0 μg in 1.0 μl) into the retrochiasmatic area of the hypothalamus can block OCH if the injections are located on the side ipsilateral to the hemi-x. This phenomenon was more apparent if the lesions and hemi-x were located on the right side. In addition, neither hemi-x nor kainic acid injections alone had any effect on vaginal cycles, whereas the combination of these two treatments reduced the incidence of estrus. However, these effects on vaginal cycles were not specifically associated with lesions or hemi-x on a particular side, thus excluding this as an explanation of the different endocrine effects of kainic acid on the two sides of the brain. These results support the evidence for a direct neural contribution to endocrine control and further suggest a functional difference in the two-halves of the hypothalamus in neuroendocrine regulation.     

Feeding and body temperature in the rat: Diencephalic localization of changes produced by excess calcium ions

In the unanesthetized rat, Ca⁺⁺ ions in solutions ranging from 2.6 to 112.0 mM in excess of the normal level in CSF were applied at different sites in the brain and by three separate procedures. Colonic temperature was monitored and in certain experiments, the amount of food pellets and water consumed was measured simultaneously following the administration of excess Ca⁺⁺ ions. An infusion into the lateral cerebral ventricle of excess calcium in a volume of 5.0 μl produced a concentration-dependent hypothermia. This fall in temperature was not attenuated by a prior intraventricular infusion of mecamylamine and often enhanced by atropine. Depending on the site, a microinjection of excess Ca⁺⁺ ions in a volume of 0.5 to 1.0 μl directly into the hypothalamus produced hypothermia or feeding. The sites of maximum sensitivity at which excess calcium caused a decline in temperature were clustered in the caudal hypothalamus, whereas those at which calcium elicited feeding were distributed widely in caudo-lateral, medial and rostral hypothalamic areas. Push-pull perfusions at a rate of 20 to 25 μl per min for 10 to 20 min at homologous sites caused similar responses but the cation concentration required to evoke feeding or hypothermia was significantly less than that of either microinjection or intraventricular infusion. These findings demonstrate species continuity in the rat concerning anatomical localization of the postulated set-point mechanism for body temperature. Several different pathways in the feeding system are affected by an alteration in the hypothalamic level of calcium.     

Interaction of alpha-MSH and MIF-I with amphetamine on open-field behavior of rats.

Forty-two albino rats were injected for 3 successive days with either α-MSH, MIF-I or a vehicle solution and then tested for activity and hind-leg rearing in the open field. On Days 4, 5 and 6 half of the animals received additional injections of d-amphetamine in 3 different doses or a vehicle solution. Only d-amphetamine influenced activity with the largest dose exerting the greatest effect. Increases in activity after treatment with the combination of d-amphetamine and α-MSH was significant. Hind-leg rearing was potentiated by injections of both d-amphetamine and α-MSH while the injection of these substances alone had negkigible influences on behavior. The results indicated that although α-MSH and d-amphetamine influence different behaviors they may interact to potentiate some behaviors. The results suggest that α-MSH and d-amphetamine may affect similar sites in the brain.     

Hypothalamic Na and Ca ions and temperature set-point: New mechanisms of action of a central or peripheral thermal challenge and intrahypothalamic 5-HT, NE, PGE1, and pyrogen

The effects of changes in ambient and central temperature, amines, PGE₁ and pyrogen were investigated with respect to the mechanism of Na⁺−Ca⁺⁺ ratio in the posterior hypothalamus of the unrestrained cat. Guide tubes were implanted bilaterally above the posterior hypothalamic area of 23 cats so as to accommodate push-pull cannulae. After a Na⁺ or Ca⁺⁺ sensitive site was identified by perfusion at 50 μ1/min of an artificial CSF containing 10.4 mM excess Ca⁺⁺ ions or 13.6 mM excess Na⁺ ions, several types of experiments were undertaken with the results summarized as follows: if the cat was exposed to a cold or warm environmental temperature as the posterior hypothalamus was perfused with excess cation, the typical hypothermia was produced by Ca⁺⁺ and hyperthermia by Na⁺ ions. However, if the cat was exposed to peripheral cooling or warming 30 min prior to the perfusion, the fall or rise produced by Ca⁺⁺ or Na⁺ was attenuated or prevented. In other experiments, 1.0 μCi ^{4 5}Ca⁺⁺ was injected in the ion sensitive site in the posterior hypothalamus to label stores of the cation. Raising of ambient temperature caused a retention of ^{4 5}Ca⁺⁺ in this hypothalamic area, whereas a cold environmental temperature enhanced the efflux of ^{4 5}Ca⁺⁺ at the same perfusion site. The magnitude of change in ^{4 5}Ca⁺⁺ efflux depended upon the intensity of the thermal challenge. Similarly, warming of the anterior hypothalamic, preoptic area by means of implanted thermodes caused an immediate diminution in ^{4 5}Ca⁺⁺ efflux in the posterior hypothalamus, whereas cooling of this anterior region augmented the extrusion of ^{4 5}Ca⁺⁺ ions from the posterior area. When substances which produce a temperature change were applied to the same thermosensitive zone, the direction of shift in ^{4 5}Ca⁺⁺ flux in the posterior area corresponded to the signal for heat production or heat loss. That is, the microinjection of 5-HT, PGE₁, or Salmonella typhosa into the anterior hypothalamus enhanced the efflux of ^{4 5}Ca⁺⁺ in the posterior hypothalamus as hyperthermia developed, whereas a similar microinjection of norepinephrine reduced the ^{4 5}Ca⁺⁺ output from the same sites. Finally, locally anesthetizing the cells of the anterior hypothalamus by the nerve blocker, procaine, prevented the cold and heat-induced ^{4 5}Ca⁺⁺ efflux and retention, respectively. These results suggest that if the Na⁴−Ca⁺⁺ ratio in the posterior hypothalamus establishes and maintains the set-point for body temperature of 37°–38°C, the mechanism of lability of Ca⁺⁺ through changes in binding characteristics, transport, or metabolism of the cation serves two purposes: (1) the active defense of the set-point temperature through gradations in ion shifts; and (2) the upward or downward change in set-point value, pathological or normal, triggered by virtue of impulses relayed from the anterior hypothalamus.     

Copper-induced release of immunoreactive α-melanotropin from isolated hypothalamic granules

Previously, we demonstrated that copper chelates stimulate the release of luteinizing hormone releasing hormone (LHRH) from isolated hypothalamic granules. To assess the generality of the copper-stimulated release process, we determined the effects of copper on the release of immunoreactive α-melanotropin (α-MSH₁) from isolated granules. When granules were incubated with various copper complexes, CuATP stimulated α-MSH₁ release by 54 ± 6% (mean ± S.E.), Cu tartarate by 56 ± 4%, CuBSA by 32 ± 5% and Cu histidine by 29 ± 2%. CuATP-stimulated α-MSH₁ release from granules incubated under N₂ was 57% of that incubated under air. Furthermore, the reducing agent dithiothreitol (DTT) inhibited CuATP-stimulated α-MSH₁ release (p < 0.01), whereas oxidized DTT did not do so. Pretreatment of granules with the thiol-blocking reagents iodoacetic acid or 5, 5'-dithiobis-(2-nitrobenzoic acid) inhibited CuATP-stimulated α-MSH₁ release by 52 ± 3 and 38 ± 4%, respectively. Thus, chelated copper, rather than ionic copper, is the active form of the metal and the action of copper involves the oxidation of thiols. These data are similar to those previously observed for the copper-stimulated release of LHRH. Hence, the effects of copper on the permeability of granule membranes may be a generalized phenomenon which underlies susceptibility of storage granules to the reduction-oxidation status of the cellular milieu.     

Influence of hypothalamic deposits of antidipsic drugs on renal excretion

Antidipsic drugs, implanted bilaterally into the rat hypothalamus affected urine excretion. Urine volume was augmented and the osmolarity lowered, as compared to controls with hypothalamic talc deposits and deprived of water. The possibility that both effects, adipsia and polyuria, may result from inhibition of hypothalamic osmoreceptor function is discussed.