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Biomedical subjects

R G Dyer

Publications and source records attributed to R G Dyer.

At least 19 recordsLinked to original sources

Opioid binding in the rostral hypothalamus is reduced following lesion of the ventral noradrenergic tract in female rats.

Experiments were undertaken to establish whether opioid receptors exert a direct presynaptic influence on noradrenergic (NA) terminals in the preoptic/anterior hypothalamus (PO/AH) of the female rat. Thus, opioid binding studies were performed in rats with lesions of the ventral NA tract (VNAT; the main NA projection to the hypothalamus) to assess whether a loss of NA terminals may also result in a decrease in opioid binding in the PO/AH. In the first experiment, unilateral electrolytic lesions of the VNAT caused a significant reduction in both the NA content and specific [3H]-diprenorphine binding to membrane homogenates in the ipsilateral PO/AH. In the second experiment bilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the VNAT caused a significant reduction in NA levels in the PO/AH as well as significant decreases in the density of [3H]-diprenorphine binding to tissue sections of the PO/AH when compared to control animals. These results strongly suggest that the NA input to the PO/AH is regulated by endogenous opioid peptides, and provide an anatomical substrate to explain opioid-NA interactions in the control of gonadotrophin releasing hormone (GnRH) and gonadotrophin secretion.

Animals

Role of medial preoptic GABA neurones in regulating luteinising hormone secretion in the ovariectomised rat.

The role of GABA neurones in the medial preoptic area (MPOA) in regulating the activity of the luteinising hormone-releasing hormone (LHRH) neurones projecting to the median eminence was investigated in the conscious ovariectomised rat. Plasma luteinising hormone (LH) concentrations were measured while (1) endogenous GABA release from the MPOA was monitored with the technique of microdialysis, or (2) activity at the GABA receptor was modulated by local infusions into the MPOA. Microdialysis studies revealed a fluctuating level of GABA release in the MPOA which did not correlate with pulsatile LH secretion. Infusion of 10 microM GABA (n = 8) or bicuculline methiodide (BMI, n = 6) into the MPOA, at a rate of 1 microliter/30 min, significantly inhibited mean LH concentrations (P less than 0.05-0.001) and LH pulse frequency (P less than 0.05-0.001) compared with controls (n = 8). LH pulse amplitude was not significantly altered by infusion of GABA (P greater than 0.05) while too few pulses were found after BMI treatment to enable statistical analysis. Infusions of GABA into the ventral half of the MPOA had a more significant inhibitory effect upon LH secretion compared with dorsal infusions (P = 0.012). A similar relationship did not exist for BMI infusions. These results show that acute changes in preoptic GABA receptor occupancy result in disruption of pulsatile LH secretion in the ovariectomised rat. This suggests that GABA neurones provide a tonic input important for the functional integrity of the neural network controlling LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effect on luteinizing hormone secretion of GABA receptor modulation in the medial preoptic area at the time of proestrous luteinizing hormone surge.

Using a bilateral medial preoptic area (MPOA) infusion system in conscious female rats we have investigated the role of the GABA system in this area on the proestrous luteinizing hormone (LH) surge. Fifteen-minute blood samples for LH estimation were taken throughout the afternoon of proestrus from female rats exhibiting 4-day oestrous cycles and implanted at least 2 weeks prior with cerebral guide cannulae. Between 15:00 and 17:00 h rats received an infusion (1 microliter/30 min) of artificial cerebrospinal fluid (n = 7), 10 microM GABA (n = 6) or 10 microM bicuculline methiodide (BMI, n = 6). Animals infused with GABA failed to exhibit an LH surge, while BMI-treated animals displayed an LH surge which was not significantly different to controls. These data show that on the afternoon of proestrus, there are no tonic modulatory actions of the GABA system, acting through the GABAA receptor, on neural elements controlling the LH surge in the MPOA. If, however, GABA levels are elevated in the MPOA at this time then the LH surge is blocked. In conjunction with data from correlative studies showing a decrease in endogenous GABA release prior to the LH surge, we suggest that this fall in activity is an essential component of the LH surge mechanism.

Animals

A method for recording single unit activity from the brains of foetal pigs in utero.

A technique is described for recording single unit activity from foetal miniature pigs in utero. The method involved anaesthetizing the sows with halothane and exteriorizing a sufficient length of the uterus to contain a single foetus. Both foetus and uterus were placed in a stereotaxic frame which was held independent of the mothers' support. Preliminary analysis of recordings obtained from spontaneously firing single nerve cells in the post-central cerebral cortex indicate that the patterns of spike activity in prenatal pigs are very similar to those observed in prepubertal animals.

Animals

Inhibition by pentobarbitone and urethane of the in vitro response of the adenohypophysis to luteinising hormone-releasing hormone in male rats.

1 The effect of urethane (ethyl carbamate) and sodium pentobarbitone on the luteinising hormone-releasing hormone (LH-RH)-stimulated secretion of luteinising hormone (LH) was investigated with hemipituitaries obtained from male rats and incubated in vitro. 2 Urethane and pentobarbitone were added to the incubation medium to provide final concentrations of 2.2 mg or 4 micrograms/ml and 100 micrograms or 0.1 microgram/ml respectively. The high doses of these anaesthetics blocked the LH-RH stimulated secretion of LH. The low doses significantly reduced the amounts of LH released in response to LH-RH but did not block the response completely. 3 Both concentrations of urethane reduced the basal release of LH. 4 The inhibitory action of the anaesthetics was reversible. 5 The results indicate that the two anaesthetics most commonly used in neuroendocrine experiments have a significant inhibitory action on the release of LH from the adenohypophysis.

Animals

Electrochemical deposition of iron onto rat oxytocinergic neurones does not result in milk-ejection.

Exposure of the preoptic-tuberoinfundibular system to iron ions causes ovulation in the pro-oestrous rat. This electrochemical treatment has been used frequently to study the way that the hypothalamus triggers secretion of gonadotrophic hormone and most investigators have assumed that the effect is mediated by the direct excitation of those neurones exposed to the cation. The present paper reports experiments designed to confirm that iron directly excites hypothalamic neurones to the firing frequencies essential for ovulation. Because of the difficulty of measuring input-output relationships in the diffuse preoptic-tuberoinfundibular system the experiments were performed on the anatomically distinct oxytocinergic neurones of the paraventricular-hypophysial tract in lactating rats. These neurones were simulated electrically (from 10 to 50 Hz for between 1 and 300 s) and subjected to the electrochemical treatment by depositing iron ions from the tip of the stimulating electrode (up to 250 muA anodal current for between 60 and 180 s). Changes in intramammary pressure were used to indicate oxytocin release and mammary glands were calibrated for sensitivity by intravenous injection of oxytocin. Electrical stimulation in excess of about 15 Hz invariably caused release of sufficient oxytocin to cause a rise in intramammary pressure. In contrast, no changes in pressure were observed during or after the electrochemical deposition of iron. The results suggest that the response of hypothalamic neurones to electrochemical treatment is not the same as their response to electrical stimulation.

Animals

Electrical stimulation of the hypothalamus: new observations on the parameters necessary for ovulation in rats anaesthetised with pentobarbitone during the pro-oestrous "critical period".

The experiments were designed to specifiy optimal parameters of hypothalamic electrical stimulation to induce ovulation in rats anaesthetised with pentobarbitone during the "critical period" on the afternoon of pro-oestrous. We have established that duration of stimulation in the arcuate region of the hypothalamus is of greater importance than total number of pulses delivered. The minimum period of stimulation to ensure that all rats ovulated was 45 min. However, stimulation in the arcuate region did not have to be continuous throughout this period. Indeed, three 5-min bursts at 100 Hz distributed equally through 45 min always caused ovulation whereas a continuous 15-min stimulation at the same frequency was without effect. With 30 min of continuous stimulation in the arcuate region, at frequencies ranging from 10 to 100 Hz, approximately half of the rats ovulated.

Anesthesia, General

Preovulatory secretion of gonadotrophins and TSH in cyclic rats with small lesions in the preoptic area.

Animals with unilateral or bilateral lesions, with respectively 85 and 70% of intact preoptic area tissue remaining, returned to regular oestrous cycles. By comparison with sham-operated controls, rats with lesions had more days with a leucocytic smear in each of the 1st, 2nd or 3rd post-operative cycle, before returning to a 4-day cycle. Hormone measurements of blood collected during the afternoon of pro-oestrus showed that, in rats with bilateral lesions, the duration of the preovulatory LH secretion was significantly shortened, although peak levels were unchanged; the initial phase of the preovulatory FSH secretion was lost; and much of the prolactin surge was also inhibited. The TSH surge was unaffected.

Animals

Non-random distribution of cell types in the preoptic and anterior hypothalamic areas.

1. Single units were recorded extracellularly from the preoptic and anterior hypothalamic areas of male and female rats anaesthetized with urethane. 2. The effect of single shock stimulation of both the mediobasal hypothalamus and corticomedial amygdala upon unit activity was assessed for all cells. Neurones were designated either antidromically invaded, orthodromically excited or inhibited, or non-responsive. 3. The distribution of responses among recorded cells was analysed for two groups of neurones. In one group the intercell distance was less than 100 mum and in the second group the distance was more than 1 mm. 4. For widely separated cells the connexions with the corticomedial amygdala and mediobasal hypothalamus were distributed at random. 5. In the groups of cells clustered closely together a marked structuring of connexions was apparant. In particular, there was a significant correlation between orthodromic responses from the amygdala (P less than 0-05) and cells antidromically activated and orthodromically excited by stimulation of the mediobasal hypothalamus were frequently adjacent to one another (P less than 0-02. 6. A complimentary analysis demonstrated that cells in the ventral half of the recording zone received significantly more inhibitory inputs from both the mediobasal hypothalamus (P less than 0-001) and the corticomedial amygdala (P less than 0-02) than those situated more dorsally. 7. The data provide evidence for structuring and orderliness in hypothalamic connexions that is often not apparent from descriptions of electrophysiological experiments.

Amygdala

Effects of ferrous ions on preoptic area neurones and luteinizing hormone secretion in the rat.

Ferrous ions (Fe2+) were applied by microiontophoresis of 29 neurones recordid from the forebrain of ten pro-oestrous rats. The spontaneous activity of 24 cells was reduced by Fe2+ and five units did not respond. No excitations were observed. Reproducible responses could not be obtained with ferric ions (Fe3+). Microinjection of 1 mul 200 mM-Fe2+ into the preoptic area of eight pro-oestrous rats produced a sharp increase in plasma LH levels. Similar treatment with saline was without effect. Rats anaesthetized with sodium pentobarbitone during the early afternoon of pro-oestrus ovulated overnight when injected with both Fe2+ and Fe3+. The experiments do not confirm the widely held belief that raised plasma LH levels following deposition of iron in the rostral hypothalamus result from increased firing of nerve cells.

Action Potentials