Anterior Hypothalamic Deafferentation Research Articles

Immunoreactive Substance P and LH-RH Content in Median Eminence and Pituitary Gland during Proestrus, Oestrus, Lactation and after Anterior Hypothalamic Deafferentation

Substance P (SP) and luteinizing hormone releasing hormone (LH-RH) content were measured by radioimmunoassay in median eminence of female rats, SP only in rats pituitary after decapitation on the day of oestrus (E), on the first and second day of dioestrus (D1 and D2), on the day of proestrus (P) and in "constant oestrus" (AD) caused by anterior hypothalamic deafferentation and in lactation (L). During four days of oestrus cycle the highest SP and LH-RH content of median eminence was found in dioestrus. Both during cyclic oestrus and "constant oestrus", SP and LH-RH were significantly lower than on the second day of dioestrus. These results may suggest the reciprocal functional relation of both hypothalamic peptides in the mechanism of the control of gonadotropin release. The highest LH-RH concentration of the median eminence was found in the animals on the 11th to 15th day of lactation, while the SP content in the median eminence of these animals is not significantly different from those of the remaining groups except the value for dioestrus (D2) rats. The SP content in pituitary of lactating rats was significantly higher than those of rats during cyclic or "constant oestrus".

Hypothalamic deafferentation in prepuberal beef heifers: Effects of gonadotropin-releasing hormone and estradiol benzoate on luteinizing hormone secretion

Hypothalamic control of luteinizing hormone (LH) secretion was investigated in crossbred beef heifer calves by comparing anterior (AHD), posterior (PHD), and complete (CHD) hypothalamic deafferentation with sham operated controls (SOC). Heifers ( n = 16) were fitted with an indwelling jugular catheter for 6 days before cranial surgery, and assigned randomly to treatments. Blood for radioimmunoassay of LH was collected sequentially at 15-min intervals during an 8-h period on days − 1 before and day 6 after hypothalamic deafferentation or sham operation. On the day of surgery, blood samples were collected sequentially at 15-min intervals 2 h before induction of anesthesia and throughout surgery and early recovery. Seven months after hypothalamic deafferentation, all experimental and sham operated heifers were ovariectomized and treated with vegetable oil (i.m.) plus saline (i.v.), vegetable oil plus gonadotropin releasing hormone (GnRH), estradiol benzoate (EB, 1 mg) in vegetable oil. After ovariectomy basal plasma concentrations of LH increased ( P < 0.01) compared with the low circulating hormone levels before ovariectomy. The amplitude of LH response to GnRH was greater ( P < 0.01) in CHD and PHD when compared with SOC and AHD heifers. Injection of EB failed to induce a LH surge in CHD and PHD 900–1100 min later when compared with the robust response seen in SOC and AHD heifers. Injection of EB plus GnRH elicited LH release in all deafferentated and sham operated heifers. These results indicate a transient change in LH secretion after AHD or CHD in prepuberal heifers with intact ovaries. After OVX, the integrity of the neural connection of the posterior hypothalamus is required for EB-induced LH release in beef heifers.

Prolactin secretion after hypothalamic deafferentation in beef calves: Response to haloperidol, α-methyl-ρ-tyrosine, thyrotropin-releasing hormone and ovariectomy

In ruminant species photoperiod regulates prolactin (PRL) secretion. It is hypothesized that the inhibition of PRL secretion resides in dopaminergic neurons of the medial basal hypothalamus (MBH). To test this hypothesis, anterior (AHD), posterior (PHD) and complete (CHD) hypothalamic deafferentation and sham operation control (SOC) surgeries were carried out during May (long-day photoperiod) in beef heifer calves (6–8 mo old) to measure basal PRL secretion and PRL secretion as affected by intravenous secretagogues. On the day of surgery (day 0), PRL secretion reflected stress of anesthesia and surgery in all groups. Thyrotropin-releasing hormone (TRH), α-methyl-ρ-tyrosine (αMρT), and haloperidol (HAL) was iv injected on days 11, 13 and 15, respectively. AHD, PHD, CHD, and SOC calves responded to TRH (100 μg) with an acute increase in PRL that peaked within 20 min. All heifers responded to αMρT (10 mg/kg BW) with an acute elevation in PRL within 10 min and remaining elevated for 3 h. HAL (0.1 mg/kg BW) induced an acute increase in PRL secretion in all groups, peaking within 15–30 min. Seven months later (December, short-day photoperiod) these heifers were ovariectomized. Basal plasma PRL levels were seasonally low, PRL secretion in AHD, PHD and CHD animals abruptly increased within 15 min to iv injection of 100 μg TRH to a greater amount than seen in SOC heifers. Although a biphasic effect on PRL secretion entrains under long-day and short-day photoperiods, hypothalamic deafferentation in cattle did not affect the pituitary gland's responsiveness to secretagogues.

Effect of anterior hypothalamic deafferentation on the negative feedback of gonadal steroids on luteinizing hormone pulse frequency in the ewe

Three experiments were performed to determined the effect of anterior hypothalamic deafferentation (AHD) on the inhibitory actions of estradiol and progesterone on luteinizing hormone (LH) pulse frequency in ovariectomized ewes during the anestrous season. The first experiment tested the effects of AHD on LH secretion in the absence of gonadal steroids. AHD was accomplished by a 180° knife cut (Halasz knife) placed at the posterior border of the optic chiasm (n=4). Control ewes received sham cuts or no surgery (n=6). LH pulses were monitored in blood samples taken every 12 min for 4 hr before and after surgery. AHD reduced LH pulse amplitude (pre 7.4±2.9 ng/ml; post 1.2±0.3 ng/ml), but had no effect on LH pulse frequency (pre 3.5±0.3/4 hr; post 3.3±0.3/4 hr) in ovariectomized ewes. In the second experiment all ewes were given a Silastic implant containing estradiol (1 cm long) and 2 d later bled at 12 min intervals for 4 hr before and after administration of pimozide (PIM, 0.08 mg/kg), a dopamine antagonist. Estradiol decreased LH pulse frequency in controls (2.8±0.4 to 1.5±0.3/4 hr) and this was reversed by PIM (2.5±0.4/4 hr). In contrast, estradiol did not decrease pulse frequency in AHD ewes (3.3±0.3 to 2.8±0.5/4 hr) and PIM did not increase it (2.7±0.7/4 hr). In the third experiment, all ewes were given Silastic implants containing progesterone. Progesterone decreased LH pulse frequency in controls (2.7±0.3 vs. 1.3±0.3/3 hr) and AHD ewes (2.6±0.4 vs. 1.1±0.4/3 hr) (p<.01). Ewes were bled every 12 min for 3 hr before and after administration of WIN 44,441-3 (WIN), an opioid antagonist. WIN increased LH pulse frequency in controls (pre 1.3±0.3/3 hr; post 2.3±0.3/3 hr) and AHD ewes (pre 1.1±0.1/3 hr; post 2.4±0.4/3 hr) (p<.01). These data raise the possibility that the inhibitory influence of estradiol on LH pulse frequency requires dopaminergic input from the rostral hypothalamus. In contrast, the inhibitory influence of progesterone appears to be mediated largely via opioid neurons within the medial basal hypothalamus.

Effects of transplants of fetal mediobasal hypothalamus on luteinizing hormone pulses impaired by hypothalamic deafferentation in adult ovariectomized rats.

Pulsatile luteinizing hormone (LH) secretion is impaired after posterior anterior-hypothalamic deafferentation (PAD), which separates the anterior part of the arcuate nucleus from the mediobasal hypothalamus (MBH). In the present study, we examined whether transplants of fetal brain tissue could prevent the effects of PAD. The brain tissue containing the MBH or the cerebral cortex taken from the fetal brain was transplanted into the third ventricle of ovariectomized rats. Four weeks after the brain transplantation, animals with or without the brain transplantation were subjected to PAD. One week after PAD, blood samples were collected every 6 min for 3 h through an indwelling atrial cannula. Rats bearing PAD without transplantation showed irregular pulsatile fluctuation of plasma LH, whereas LH pulses were maintained in rats bearing transplantation of the fetal MBH tissue. In rats which had been transplanted with the cerebral cortex, LH pulses were less apparent after PAD than in the MBH-transplanted or sham-deafferentated animals. No cell bodies of LH-releasing hormone (LHRH) neurons were found immunohistochemically in the MBH grafts. These results suggest that the graft containing the fetal MBH tissue maintains regular LH pulses after PAD and that the LHRH pulse generator may consist, at least in part, of a group of neurons in the MBH other than LHRH-producing neurons.

Effects of Various Types of Hypothalamic Deafferentation on Luteinizing Hormone Pulses in Ovariectomized Rats

Abstract The pulsatile luteinizing hormone (LH) secretion in chronically ovariectomized rats bearing various types of hypothalamic deafferentation was examined. Ovariectomized rats were subjected to complete, anterolateral or anterior hypothalamic deafferentation and bled every 6 min for 3 h through an indwelling atrial cannula 5 days after the brain surgery. Another group of ovariectomized animals was subjected to posterior-anterior hypothalamic deafferentation (PAD), which cut off the anterior part of the arcuate nucleus from the mediobasal hypothalamus, and bled 1, 3 or 5 weeks after the deafferentation. Coronal sections of the brain were immunostained with anti-LH-releasing hormone (LHRH) serum. The pulsatile LH secretion was observed in rats bearing anterior, anterolateral or complete hypothalamic deafferentation and these types of deafferentation did not affect the frequency of LH pulses. The mean LH level during the 3-h sampling period and the amplitude of LH pulses decreased as the incision extended postero-laterally. Rats bearing PAD showed an irregular fluctuating pattern in plasma LH concentration 1 week after PAD. Parameters of LH pulses were restored with time after PAD. This suggests that the system generating LHRH pulses severed by PAD had been reorganized. LHRH-immunopositive neuronal fibres were found in the external layer of the median eminence in the rats bearing any type of deafferentation. The present results suggest that the frequency of LH pulses could be controlled by the LHRH pulse generator, which consists of non-LHRH neurons and is located in the mediobasal hypothalamus.

The release of pituitary LH and sprouting of LH-releasing hormone (LHRH)-containing neurons after anterior hypothalamic deafferentation

The chronology of changes in plasma luteinizing hormone (LH) and the distribution of immunoreactive neuronal processes containing LH releasing hormone (LHRH-ir) were studied in the female rat after surgical interruption of anterior neural connections of the mediobasal hypothalamus (MBH). Spontaneous LH surges on the afternoon of proestrus and LH release of proestrus and LH release after estradiol benzoate (EB) followed 48 h later by progesterone (P) administration were studied in ovariectomized (OVX) rats. The maximum increase in plasma concentrations (Δ maxLH) after EBP was calculated for each rat at several intervals over 140 days. Control animals given EBP at monthly intervals after OVX had comparably largeΔ maxLH surges during the first few months of study. However, a gradual decline in controlΔ maxLH followed becoming significant 3 months after the start of the experiment. In contrast, frontal cuts (FC), which interrupted anterior MBH connections, produced an abrupt decrease inΔ maxLH surges after EBP to 11% of preoperative levels. However, during subsequent EBP trials, there was a gradual improvement in LH surges to about 50% of preoperative levels over 100 days. In some cases, individual improvement became equal to preoperative LH surge levels, in others there was no recovery. Examination of LHRH-ir nerve growth responses after FC suggested that sprouting by these peptide-containing neuronal process may have contributed to the functional improvements observed.

Maintenance of estrous cycle in female rats with anterior or posterior deafferentation of the suprachiasmatic nucleus.

The aim of the present study was to determine which of the anterior or posterior efferents of the suprachiasmatic nucleus (SCN) predominantly act for the maintenance of estrous cycle in female rats. A small knife (0.8 mm in radius) was used for anterior (ASD), posterior (PSD) and complete suprachiasmatic deafferentations (CSD). The rats subjected to CSD were divided into two groups, the first group bearing lesions on the medial preoptic nucleus (MPN; group CSD-MPN-L) and the other group bearing no lesions on the MPN (group CSD). For reference, anterior hypothalamic deafferentation (AHD) was carried out using a large knife (2.0 mm in radius). All rats with AHD or CSD-MPN-L and some of CSD rats showed persistent estrus, but all animals with ASD or PSD resumed regular estrous cycles after transient irregular periods. Ovaries of AHD, CSD and CSD-MPN-L rats contained very few, if any, corpora lutea, while the number of corpora lutea in ASD or PSD rats was not significantly different from that of sham-operated controls. Immunohistochemical examination revealed that in AHD rats LHRH immunoreactivity in the median eminence was markedly reduced as compared with that of sham-operated controls. In contrast, in ASD, PSD, CSD and CSD-MPN-L rats, the LHRH immunoreactivity in the median eminence was similar to that of sham-operated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of anterior hypothalamic deafferentation on FSH-releasing activity in the intact female hamster.

To study the role of the anterior hypothalamic area (AHA) in the control of the estrous (E) rise of follicle stimulating hormone (FSH), female hamsters were subjected to anterior hypothalamic deafferentation (D) or sham deafferentation (S) on 1500 h of proestrus (P). Serum levels of FSH and luteinizing hormone (LH) were measured by radioimmunoassay and FSH and LH releasing activities measured by bioassay in the anterior (AH) and medial basal hypothalamus (MBH) at several time periods during P and E. D did not affect serum levels of LH, whereas there was an attenuation of FSH levels during P and E. D caused an increase in FSH releasing activity in the AH within 1 h, while LH releasing activity was elevated 8 h after D. In animals with D, LH releasing activity in the MBH was elevated during P and was similar to controls during E. FSH releasing activity in the MBH increased during early E and dropped precipitously by 1400 h of E. Collectively, these data demonstrate dichotomous changes in FSH and LH releasing activities and provide further evidence for dual control mechanisms for these two gonadotropins.

Evidence for reorganization of the neuroendocrine centres regulating pulsatile LH secretion in rats receiving neonatal monosodium-L-glutamate treatment.

Previous research has shown that the combination of anterior hypothalamic deafferentation (AHD) and electrolytic lesions of the anterior part of the arcuate nuclei blocks pulsatile LH secretion in ovariectomized rats, but that neither lesion alone was effective. Furthermore, the combination of AHD with arcuate lesions produced by neonatal treatment with monosodium-L-glutamate (MSG) does not block pulsatile LH release. To distinguish between the various possible reasons for this result, AHD and electrolytic lesions of the arcuate nuclei were combined in rats which had been treated neonatally with MSG or saline of equal osmolarity. One week after brain surgery, venous catheters were installed and blood samples taken at 5-min intervals for up to 3 h for assay of plasma LH. Rats treated with MSG and bearing AHD and electrolytic lesions of the arcuate nuclei continued to show pulsatile secretion of LH. Where the electrolytic lesions were posterior and dorsal to the anterior arcuate nuclei, however, LH release was blocked whether AHD was performed or not, but only in rats treated with MSG. None of the lesion combinations blocked pulsatile LH secretion in rats treated with saline. These results suggest that neonatal MSG treatment leads to a reorganization of the hypothalamus such that the role normally played by the arcuate nuclei in the regulation of pulsatile LH secretion is taken over by other hypothalamic structures.

Subcortical pathways involved in the mediation of adrenocortical responses following frontal cortex stimulation

The purpose of this study was to identify the subcortical neural pathways which mediate adrenocortical responses following cortical stimulation. The frontal cortex was stimulated in intact rats and in animals with medial or lateral septal or preoptic lesions or with large or small anterior hypothalamic deafferentations. All the above-mentioned lesions have significantly blocked the adrenocortical responses following frontal cortex stimulation, suggesting that the above-mentioned subcortical structures are involved in the mediation of this response.

Growth hormone and prolactin secretion after hypothalamic deafferentation in pigs.

Control of growth hormone (GH) and prolactin (PRL) secretion was investigated in ovariectomized, prepuberal Yorkshire gilts by comparing the effects of anterior (AHD), complete (CHD), and posterior (PHD) hypothalamic deafferentation with sham-operated controls (SOC). Blood samples were collected sequentially via an indwelling jugular catheter at 20-min intervals during surgery and recovery from anesthesia (Day 0) and Days 1 and 2 after cranial surgery. Mean serum concentrations of GH after AHD, CHD, and PHD were reduced (P less than 0.01) when compared with SOC gilts. Furthermore, episodic GH release evident in SOC animals was obliterated after hypothalamic deafferentation. PRL concentrations in peripheral serum of hypothalamic deafferentated gilts remained similar (P greater than 0.05) to those of SOC animals. These results indicate that anterior and posterior hypothalamic neural pathways play a minor role in the control of PRL secretion in the pig in as much as PRL levels remained unchanged after hypothalamic deafferentation. These findings may be interpreted to suggest that the hypothalamus by itself seems able to maintain tonic inhibition of PRL release. In contrast, the maintenance of episodic GH secretion depends upon its neural connections traversing the anterior and posterior aspects of the hypothalamus in the pig.

Hypothalamic deafferentation and luteinizing hormone-releasing hormone effects on secretion of luteinizing hormone in prepubertal pigs.

The control of luteinizing hormone (LH) secretion was investigated in ovariectomized, prepubertal Yorkshire pigs by comparing the effects of anterior (AHD), complete (CHD), and posterior (PHD) hypothalamic deafferentation to sham-operated controls (SOC). Gilts (n = 16) were assigned randomly to treatments, fitted with an indwelling jugular catheter, and ovariectomized 2 days before deafferentation or sham-operation (Day 0). Blood for radioimmunoassay (RIA) of LH was collected sequentially at 20-min intervals for a period of 2 h before and 24, 48, 72, and 96 h after hypothalamic deafferentation or SOC. Episodic LH release after AHD or CHD was abolished (p less than 0.01), but not after PHD or SOC. Concentrations of serum LH in AHD and CHD dropped (p less than 0.01) at 24 and 48 h after surgery. Levels of LH before and after surgery in PHD and SOC were similar (p greater than 0.05). Infusion of 25 micrograms LH-releasing hormone (LHRH) i.v. at 72 and 96 h after hypothalamic deafferentation and SOC increased (p less than 0.01) serum LH to peak levels within 15 min. after infusion; LH returned to basal levels 60-80 min later. By 96 h after surgery, LH response to LH-releasing hormone (LHRH) was less in AHD and CHD as compared with the response at 72 h postinjection. Concentrations of LH in PHD and SOC were similar (p greater than 0.05) at 72 and 96 h, respectively. The results from this study clearly indicate that neural stimuli originating or traversing the neural areas rostral to the median eminence are required for secretion of LH in the pig.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of anterior hypothalamic deafferentation on thyrotropin (TSH) biosynthesis and response to TSH-releasing hormone.

The effects of hypothalamic deafferentation on TSH synthesis were studied by making cuts of 180 degrees arc in the anterior hypothalamus (n = 18) or sham cuts (n = 12) in rats. After 21 days, pituitaries were incubated with [35S]methionine (MET), [3H]glucosamine (GLCN), with or without 10(-8)M TRH for 24 h. TSH and free alpha-subunits were immunoprecipitated and analyzed by gel electrophoresis. In the deafferented group as compared to sham, MET incorporation into both subunits of secreted TSH was decreased (alpha, 96 +/- (SE) 9 X 10(3) vs. 180 +/- 20 X 10(3) dpm/mg protein; beta, 35 +/- 9 X 10(3) vs. 84 +/- 15 X 10(3) dpm/mg protein; P less than 0.05). Basal GLCN incorporation into both subunits of secreted TSH was also decreased in the deafferented group (alpha, 6.5 +/- 11 X 10(3) vs. 132 +/- 17 X 10(3) dpm/mg protein; beta, 36 +/- 8 X 10(3) vs. 101 +/- 29 X 10(3), P less than 0.05). In vitro TRH did not stimulate MET incorporation into secreted TSH in the sham controls but did in the deafferented group (alpha, 270% of basal; beta, 374% of basal; P less than 0.01). In vitro TRH increased GLCN incorporation in secreted TSH in both the sham (alpha, 253% of basal; beta, 245% of basal; P less than 0.02) and the deafferented group (alpha, 692% of basal; beta, 630% of basal; P less than 0.01). GLCN/MET ratio, reflecting relative glycosylation, did not differ for sham or deafferented groups but increased 2-fold with in vitro TRH in each group for both secreted subunits (P less than 0.01). Free alpha-synthesis and intrapituitary TSH were not altered by deafferentation or TRH. In summary, 1) anterior hypothalamic deafferentation decreases basal TSH protein and carbohydrate synthesis; 2) such deafferentation increases sensitivity to TRH stimulation of TSH synthesis, most notably apoprotein synthesis; 3) TRH increases relative glycosylation of secreted TSH in both deafferented and sham groups. These data suggest that TRH plays a significant role in regulating basal TSH protein and carbohydrate synthesis, glycosylation of TSH subunits, and subsequent bioactivity.

Effect of anterior hypothalamic deafferentation and continuous growth hormone infusion on the hepatic synthesis of α2u-globulin in the male rat

Anterior hypothalamic deafferentation and infusion of human GH (hGH) in the normal male rat caused a marked reduction in the hepatic concentration of alpha 2u-globulin, an androgen-dependent protein. Although s.c. injections of hGH (twice-daily) resulted in more than a 50% reduction in the hepatic level of alpha 2u-globulin, the same dose of hGH when administered continuously through osmotic minipumps caused a threefold greater inhibition. The decreased hepatic concentration of alpha 2u-globulin after hGH administration was associated with corresponding changes in the hepatic level of translatable alpha 2u-globulin messenger RNA. Continuous infusion of hGH through osmotic minipumps and removal of the anterior hypothalamic influence on GH secretion by deafferentation also caused a marked reduction in the cytoplasmic androgen-binding activity of the rat liver. These results suggest that alterations in the level and pattern of GH secretion may influence hepatic androgen-binding activity and alpha 2u-globulin synthesis.

Effects of anterior hypothalamic deafferentation and neonatal monosodium-L-glutamate treatment on pulsatile LH secretion in the castrated rat.

Previous research has shown that electrolytic lesions of the anterior arcuate nuclei combined with anterior hypothalamic deafferentation (AHD) blocked pulsatile luteinizing hormone (LH) release in the ovariectomized rat, but that neither lesion was sufficient by itself. This led to the hypothesis that two separate neural pathways were capable of effecting pulsatile LH secretion, which was tested in another way in the present study. Newborn rats were injected with monosodium glutamate (MSG), a treatment which damages the arcuate nuclei, or NaCl of the same osmolarity as a control. As adults, the rats were gonadectomized and 2 weeks later, AHD or sham AHD was performed. One week after that, the rats were catheterized, and small blood samples were taken every 5 min for 3 h. Plasma was assayed for LH by radioimmunoassay. Neither MSG alone, AHD alone, nor the combination affected the number of animals with pulsatile LH patterns. In female rats, MSG treatment slightly decreased pulse frequency, while AHD depressed mean LH levels in male rats. No differences were seen in LH pulse amplitude. These results suggest either that MSG spares those neurons of the arcuate nuclei which are important for LH secretion, that electrolytic lesions of the arcuate nuclei destroy fibres of passage which are important for LH release, or that functional reorganization of the systems controlling LH release occurs following neonatal MSG treatment.

Reproductive failure due to experimentally induced constant estrus does not alter the LH-RH fiber density in the median eminence of the rat.

The effects of anterior hypothalamic deafferentation on luteinizing hormone releasing hormone (LH-RH) fiber density in the mediobasal hypothalamus (MBH) were compared to those of a number of nonsurgical treatments which give rise to anovulatory sterility (injections of estradiol valerate, exposure to constant light, or neonatal androgen administration) in the female rat. All of the treatments used (surgical and nonsurgical) disrupted the normal 4-day pattern of estrous cyclicity. Bilateral anterior hypothalamic deafferentation markedly reduced the packing density of LH-RH fibers in the MBH. Unilateral deafferentation reduced the number of fibers on the ipsilateral side of the MBH by 31-64% and on the contralateral side by 15-40%. In contrast, none of the three nonsurgical treatments had any significant effect on the LH-RH fiber density. Electron microscopic examination revealed no morphologic, or distribution differences in MBH LH-RH fibers between control females and animals rendered anovulatory by the nonsurgical experimental procedures. These results demonstrate that estrogen, androgen, and constant light induced anovulatory sterility are not associated with any overt change in the number or morphology of LH-RH immunoreactive fibers in the MBH, suggesting that the primary lesion responsible for the failure of normal estrous cyclicity in such animals resides in the systems responsible for regulating the activity of the LH-RH neurons rather than in the LH-RH neurons themselves.

Modifications of adrenocortical responses following frontal cortex simulation in rats with hypothalamic deafferentations and medial forebrain bundle lesions

With the purpose of delineating the neural pathways in the rat which mediate adrenocortical responses following frontal cortex stimulation, the effects of partial hypothalamic deafferentations and medial forebrain bundle lesion were studied. In intact and sham-operated animals, cortical stimulation through permanently implanted electrodes caused a significant increase in plasma corticosterone levels. In rats with anterior hypothalamic deafferentation and bilateral medial forebrain bundle lesions the adrenal response to cortical stimulation was blocked completely, while in animals with posterior hypothalamic deafferentation there occurred a normal rise in plasma corticosterone. These studies demonstrate that the frontal cortex effects on adrenocortical secretion are neurally mediated and involve an anterior hypothalamic input, more specifically the medial forebrain bundle.

Factors that influence test session performance measured 0, 3, or 6 h after inhibitory avoidance training

Rats were trained in a step-down inhibitory avoidance task using a 0.3-mA, 60-Hz footshock, and were tested at 0, 3, and 6 h from training. Retrieval scores (test session minus training session step-down latencies) were higher in control groups at 0 than at 3 or 6 h. Test session performance at 0 h was unaffected by the pretraining ip injection of ACTH1-24 (0.2 microgram/kg), epinephrine-HCl (5.0 micrograms/kg), human beta-endorphin (1.0 microgram/kg), or naloxone-HCl (0.4 mg/kg); or by a pretreatment with dexamethasone phosphate (2.0 mg/kg in divided doses 24 and 12 h before training); or by anterior or posterior hypothalamic deafferentation. Test session performance at 0 h was depressed by prior bilateral transection of the fornix, which suggests it depends on hippocampal function. The effect of the fornix lesion on test session performance at 0 h was not counteracted by ACTH, epinephrine, or beta-endorphin administration. When animals were tested 3 h after training, the post-training administration of ACTH and epinephrine caused an enhancement of test session performance; neither post-training beta-endorphin or naloxone, nor pretest ACTH, epinephrine, or beta-endorphin administration, had any effect in these animals. At 6 h from training, the post-training facilitatory action of ACTH and epinephrine was still present and the post-training depressant effect of beta-endorphin and the post-training facilitatory effect of naloxone became manifest, and so did the naloxone-reversible pretest facilitation induced by ACTH, epinephrine, or beta-endorphin. The influence of post-training naloxone or pretest beta-endorphin on retrieval scores at 6 h was not observed in the fornix-lesioned animals. Test session performance of this task at 0 h from training is regulated by different mechanisms than those which regulate test session performance at 3 or 6 h; in particular, it is less susceptible to modulation by the drugs used in the present study and it depends on the fornix; At least two major classes of modulatory factors influence retrieval scores at later times: consolidation-enhancing effects of ACTH and epinephrine, which become manifest at 3 h, and mechanisms related to beta-endorphin, which involve a form of state dependency and only become manifest at 6 h from training.

Posterior hypothalamic deafferentation abolishes the amnestic effect of electroconvulsive shock in rats

The amnestic effect of immediate post-training transcorneal electroconvulsive shock ECS (15.0 mA, 60 Hz, 2 sec) on step-down inhibitory avoidance learning (0.5 mA, 60 Hz training footshock) was studied in intact rats and in rats submitted to bilateral surgical transection of the dorsal fornix, to anterior or posterior hypothalamic deafferentation, and in sham-operated animals. Animals were tested for retention 24 hr after training. The amnestic effect of ECS was observed in all groups except in the one with the posterior hypothalamic lesion. Fornix-lesioned animals showed a moderate retention deficit which was considerably worsened by the ECS treatment. The results indicate that the amnestic effect of ECS requires integrity of posterior hypothalamic pathways. One possibility is that the amnestic effect of ECS may be mediated by posterior afferent fibers to the hypothalamus acting on hypothalamic opioid systems such as have been previously proposed to play a role in ECS-induced amnesia.