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K J Renner

Publications and source records attributed to K J Renner.

35 records · Page 2Linked to original sources

Corticosterone-dependent alterations in utilization of catecholamines in discrete areas of rat brain.

This study investigated the impact of chronic adrenalectomy (ADX), and subsequent corticosterone (CORT) replacement to ADX rats, on brain levels of norepinephrine (NE) and dopamine (DA) and their extent of depletion after alpha-methyl-p-tyrosine (alpha-MpT) administration. Seven discrete hypothalamic areas, namely, the paraventricular nucleus (PVN), medial preoptic nucleus (POM), dorsomedial nucleus (DMN), ventromedial hypothalamus (VMH), perifornical lateral hypothalamus (PLH), supraoptic nucleus (SON), and arcuate nucleus/median eminence (ARC-ME), were examined. The steady-state content of NE and DA in all areas remained essentially unaltered 7 days after ablation of the adrenal glands, as well as after subsequent CORT replacement therapy in ADX rats. However, ADX, which reduced circulating CORT levels to 0.3 microgram % as compared to greater than 3.0 micrograms % in sham rats, caused a significant increase in the depletion of NE following alpha-MpT treatment, in 4 out of the 7 brain sites examined (PVN, PLH, DMN and ARC-ME). In these brain sites, the NE turnover rate (K, pg/microgram protein/h) and rate constant (K, h-1) increased following ADX. The chronic subcutaneous CORT implant (200 mg), which raised circulating CORT levels of ADX rats to 11 micrograms %, prevented this enhancement of NE turnover in the PVN, PLH and ARC-ME, but not the DMN. Unlike NE, DA utilization in the 7 discrete hypothalamic areas of alpha-MpT-treated rats remained unaltered after ablation of the adrenal glands, as well as after the CORT replacement therapy in ADX rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

Spreading depression induced by 100 mM KCl in caudate is blocked by local anesthesia of the substantia nigra.

Pressure-ejection of 100 mM KCl was used to induce voltammetric signals in the rat caudate. The signals, detected chronoamperometrically with Nafion-coated carbon fiber microelectrodes, were reproducibly generated at 20-min intervals up to distances of 1600 micron from the KCl stimulus site. Unilateral 6-hydroxydopamine lesions of the substantia nigra (SN) demonstrated that over 90% of the voltammetric signal generated was dopamine. Evaluation of the signal onset at two widely spaced electrodes suggested that injection of nl volumes of 100 mM KCl into the rat caudate generates voltammetric signals which resemble spreading depression (SD) produced by more classical methods (e.g. 1 M KCl). We further investigated this phenomenon by simultaneous evaluation of extracellular K+ ion concentration changes, field potential (FP) and voltammetric signals or multiunit activity following stimulation with 100 mM or 1 M KCl. The results show that the signals generated by 100 mM KCl have many of the attributes of 'classical' SD, although the extracellular K+ ion concentration changes and FP changes were smaller in magnitude. However, the characteristic burst of multiunit activity followed by a marked quiescent period found during 1 M KCl stimulation was not observed with 100 mM KCl stimulation. Furthermore, application of 0.5% lidocaine to the SN reversibly blocked all signals generated by 100 mM KCl in the caudate while similar treatment with up to 2% lidocaine was ineffective when 1 M KCl was used as the stimulus. The results suggest that the signals generated by 100 mM KCl may represent an attenuated form of SD which requires a functioning SN, and that this stimulation could be a useful model for studying neurotransmitter interactions in the propagation of the SD phenomena.

Action Potentials↗

Electrocoating carbon fiber microelectrodes with Nafion improves selectivity for electroactive neurotransmitters.

A method which improves carbon fiber microelectrode selectivity for cationic amines by electrocoating the fiber with a thin film of the ionic polymer, Nafion, is described. The selectivity and response speed of these electrodes for the detection of electroactive cationic and anionic species found in brain extracellular fluid was evaluated using differential pulse voltammetry and chronoamperometry and compared to uncoated fibers. Carbon fiber microelectrodes electrocoated with Nafion are highly sensitive to cationic amines such as dopamine and serotonin and have minimal sensitivity to anions such as ascorbic acid and uric acid at physiological concentrations.

Carbon↗

Noradrenergic regulation of alpha 1-receptors during the postnatal development of the guinea pig.

In guinea pig brain, alpha 1-noradrenergic receptor concentrations undergo region-specific fluctuations during the first weeks of postnatal life. However, the factors involved in the regulation of these receptors have yet to be identified. In this study, the ontogeny of one possible regulatory factor, norepinephrine, was examined in relation to postnatal changes in alpha 1-receptor levels in several different regions of guinea pig brain. Results from these studies showed that while the activity of the noradrenergic system increased throughout the first weeks of postnatal development in each brain area examined, the concentration of alpha 1-receptors decreased in preoptic area and hypothalamus and increased in cortex. In subsequent experiments, the effects of noradrenergic lesions with 6-hydroxydopamine on alpha 1-receptor levels were assessed to examine the possibility that alpha 1-receptors are differentially sensitive to noradrenergic stimulation in cortex and preoptic area/hypothalamus in immature guinea pigs. Noradrenergic lesions which reduced norepinephrine levels by 87-94% resulted in significant elevations in alpha 1-receptors in all regions examined. These results are discussed with reference to the anatomical distribution of alpha 1-receptors and their regulation by norepinephrine.

Animals↗

Effect of progesterone on monoamine turnover in the brain of the estrogen-primed rat.

The effect of progesterone (P) on monoamine levels and turnover was evaluated in 8 brain nuclei in estrogen-primed rats. Animals were subcutaneously (SC) injected with P or vehicle 21 hours after SC treatment with 5 micrograms of estradiol benzoate (EB). EB-primed animals treated with P showed high levels of lordosis behavior and an LH surge three hours later. Initial concentrations of norepinephrine (NE), dopamine (DA), serotonin (5HT) and 5-hydroxyindole acetic acid were determined in EB-saline treated controls 3 hours after P or vehicle. NE and DA turnover was estimated from the exponential decline of these amines 2 hours after IP injection of alpha-methyl-p-tyrosine (5 hours after P or vehicle). The accumulation of 5HT 20 min following IP injection of pargyline was used as an index of 5HT turnover. P did not affect the initial NE, 5HT or 5HIAA concentrations in any of the brain nuclei studied, but decreased DA content in the arcuate-median eminence region (Ar-ME). The DA rate constant was elevated in the nucleus of the diagonal band of Broca and the DA turnover rate was decreased in the Ar-ME. In the periventricular region (PVE, anterior hypothalamic level) the NE turnover rate (K, pg/microgram protein/hr) and rate constant (k, hr-1) decreased following P treatment. Progesterone treatment decreased the accumulation of 5HT in the ventromedial hypothalamus (VMN, pars lateralis) and the dorsal midbrain central grey (MCG). Progesterone effects on monoamine turnover were not found in the lateral septal, medial preoptic, anterior hypothalamic or dorsal raphe nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Lesions in the preoptic area suppressed sexual receptivity in ovariectomized rats with estrogen implants in the ventromedial hypothalamus.

The objective of the experiment was to determine if electrolytic ablation of a portion of the preoptic area (POA) influenced the activation of female lordosis behavior by implants of estradiol benzoate in the ventromedial hypothalamus (VMH) of ovariectomized (OVX) rats. Two weeks after ovariectomy, rats received either bilateral electrolytic lesions (2 mA for 10 sec in Experiment 1, or 1 mA for 5 sec in Experiment 2) in the POA, or sham lesions (all procedures except passage of current). On the same day (day 0 of the experiment) thirty-gauge stainless steel cannulae containing crystalline estradiol benzoate were stereotaxically placed bilaterally into the VMH of all the rats. Subsequently, females were tested for the lordosis response to stud males on days 2, 4, 6, 8, and 10 in Experiment 1 or on days 7, 14 and 15 in Experiment 2. All rats received 0.5 mg progesterone (SC) only before the last test. A female was considered sexually receptive if she exhibited a lordosis quotient (LQ) greater than or equal to 10 (LQ = No. lordosis responses/10 mounts by male X 100). The frequencies for sexual receptivity in females with POA lesions were significantly lower than those for control females without lesions in both experiments. Additionally the degree of receptivity (lordosis quotient) was significantly lower on each test day for rats with POA lesions than that for rats without POA lesions. The results imply that the maintenance of the integrity of the POA under this experimental condition was important for the expression of the facilitative influence of the VMH on lordotic responsiveness.

Animals↗

Monoamine levels and turnover in brain: relationship to priming actions of estrogen.

Norepinephrine (NE), dopamine (DA) and serotonin (5HT) levels and turnover rates were studied in 8 discrete brain nuclei of ovariectomized rats 24 hours after the administration of 5 microgram of estradiol benzoate (EB) or sesame oil vehicle. This estrogen paradigm, by itself, did not induce sexual behavior or alter LH levels at the time these parameters were evaluated. However, combined with progesterone, the estrogen treatment was sufficient to generate an LH surge and induce sexual receptivity. Steady state concentrations of NE were significantly higher in the diagonal band of Broca (NDB) and the periventricular nucleus (PVE2; anterior hypothalamic level) following EB treatment. In addition, 5-hydroxyindole acetic acid (5HIAA) concentrations were elevated in the dorsal raphe of EB treated animals. Estrogen did not affect steady state concentrations of DA or 5HT in any of the brain nuclei studied. Turnover rates (K, pg/microgram protein/hr) and rate constants (k, hr-1) for NE were increased in the lateral septum (K, 140%; k, 120%), NDB (K, 160%; k, 130%) and the PVE2 (K, 140%; k, 70%) in EB treated animals. Estrogen decreased the rate constant for NE by 30% in the medial preoptic area. In contrast, DA and 5HT turnover rates were not significantly affected by estrogen. These results localize sites where estrogen induces changes in noradrenergic activity and suggest that these changes may be involved in the priming action of the steroid in inducing sexual behavior and/or gonadotropin secretion.

Animals↗

Sex-dependent differences in estrogen regulation of choline acetyltransferase are altered by neonatal treatments.

We investigated whether estrogenic actions of testosterone during development which mediate the suppression of feminine reproductive behavior and cyclic gonadotropin secretion also contribute to reported sex differences in the induction of choline acetyltransferase (ChAT) after estrogen priming in the diagonal band region of the preoptic area. Newborn female rats received estradiol (E2 females); newborn males received 1,4,6-androstatrien-3,17-dione (ATD), an inhibitor of aromatase (ATD males); and some of both sexes received vehicle treatment (control). In adulthood, feminine sexual behavior (lordosis) was tested after E2 plus progesterone priming. The neonatal treatments reversed the sex-specific response pattern; E2 females were defeminized and displayed minimal lordosis, as did control males, while ATD males showed maximal lordosis, as did control females. E2 was then administered, and ChAT activity was measured in the horizontal and vertical nuclei of the diagonal bands (hDB and vDB, respectively). Controls exhibited the normal sex-specific response to E2. Females showed increased ChAT activity in the hDB and unaltered activity in the vDB: males had unaltered ChAT activity in the hDB and decreased activity in the vDB. In neonatally treated males and females, ChAT activity after E2 administration was not altered from the normal sex-specific pattern in the hDB, i.e. all females showed increased hDB ChAT after E2, and no male responded. In the vDB, groups defeminized in terms of lordosis (E2 females and control males) showed higher ChAT activity in the absence of E2 priming, and E2 treatment decreased vDB ChAT in these groups. In addition, ATD males showed a unique response to E2 in the vDB, namely increased ChAT activity. Although neonatal E2 and ATD treatments did not completely reverse the sex-specific pattern of E2 priming on ChAT activity, the results obtained suggest that a net increase in diagonal band cholinergic function, as indexed by increased ChAT activity after E2 priming, may contribute to the ability of hormones to induce lordosis and/or LH surges.

Androstatrienes↗

Sex differences in long-term gonadectomized rats: monoamine levels and [3H]nitroimipramine binding in brain nuclei.

The levels of norepinephrine, dopamine, serotonin and the serotonin metabolite 5-hydroxyindoleacetic acid were measured in microdissected brain nuclei from long-term gonadectomized male and female rats. Females had 50 and 120% higher levels of serotonin in the anterior hypothalamic nucleus (AH) and arcuate-median eminence (AR-ME), respectively. No significant differences in norepinephrine, dopamine or 5-hydroxyindoline acetic acid were found in any of the brain nuclei sampled. The differences in serotonin content do not appear to result from a sexually dimorphic distribution of serotonin nerve terminals since quantitative autoradiography of 3H-nitroimipramine revealed no differences in binding between the sexes in the AH or AR-ME.

Animals↗

Naltrexone facilitation of sexual receptivity in the rat.

Naltrexone hydrochloride (3mg/kg) facilitated sexual receptivity in ovariectomized female rats given estradiol benzoate 44 hr previously. The latency of naltrexone facilitation is 3 hr, which is similar to that by progesterone. Other doses of naltrexone (1 and 5 mg/kg) were ineffective. Unlike the effect of progesterone, the facilitation of behavior by naltrexone is not blocked by the protein synthesis inhibitor anisomycin. Naltrexone facilitation was blocked by pargyline, a monoamine oxidase inhibitor.

Adrenalectomy↗

Facilitated sexual behavior reversed and serotonin restored by raphe nuclei transplanted into denervated hypothalamus.

Fetal raphe cells transplanted into the hypothalamus reversed facilitation of feminine sexual behavior in rats with brain lesions induced by 5,7-dihydroxytryptamine. Immunocytochemical and chemical analyses of serotonin indicate that reinnervation of the ventromedial nucleus of the hypothalamus by the transplants is associated with behavioral recovery. The findings suggest that transplanted fetal tissue can exert functional regulation over an innate, complex, hormone-dependent behavior in adult rats.

5,7-Dihydroxytryptamine↗

Determination of monoamines in brain nuclei by high performance liquid chromatography with electrochemical detection: young vs. middle aged rats.

A previously described high performance liquid chromatographic method for simultaneously measuring norepinephrine, dopamine, serotonin and 5-hydroxyindole acetic acid has been modified to permit analysis of the monoamines in microdissected brain nuclei from a single rat. Results of measurements in 12 nuclei of young and middle aged male rats are presented.

Aging↗

Suppression of sexual behavior and localization of [3H] puromycin after intracranial injection in the rat.

Bilateral intracranial injections of puromycin (10 micrograms/0.5 microliter vehicle) into the preoptic area (POA) of steroid-primed ovariectomized rats resulted in a significant decrease in the lordosis response when compared to saline treated controls. To determine the extent of puromycin diffusion after intracranial injection, [3H] puromycin was injected into the right POA of ovariectomized rats. Neural regions anterior, posterior and superior to the POA, and the right and left POA were assessed for tritium activity 0.5, 6 and 24 hours after stereotaxic surgery. The activity was primarily located at the injection site or in the injection tract. The highest amount of activity external to the injection site or injection tract was found in the right ventromedial hypothalamus.

Animals↗

Brain catecholamine content during the estrous cycle and in steroid-primed rats.

Norepinephrine (NE) and dopamine (DA) levels were measured in several estrogen concentrating brain regions over the estrous cycle and in steroid-primed ovariectomized rats under experimental conditions used to study sexual receptivity. Norepinephrine content in the ventromedial hypothalamus (VMH), lateral septum (LS) and medial preoptic area (POA) varied during the estrous cycle. The highest NE levels were found during metestrus in these brain regions. In the ovariectomized rat, NE levels were increased in the POA and LS 12 hours (hr) after the injection of 3 micrograms of estradiol benzoate (65% and 33%, respectively). Norepinephrine content in the POA and LS remained elevated 24 hr and 48 hr (0.5 mg progesterone at 42 hr) after treatment but were not different from control levels at 96 hr. Dopamine concentrations were not significantly altered over the estrous cycle or by the administration of estradiol benzoate in any of the brain regions studied. These results suggest that estrogen may selectively alter noradrenergic activity in brain regions that are implicated in the control of sexual receptivity and/or ovulation.

Amygdala↗

Cycloheximide activation of the lordotic response in low-dose, estrogen-treated ovariectomized rats: evidence for modulating inhibitory influences of the limbic system on sexual behavior.

This study tested the effect on intracranially injected cycloheximide (CHX), an inhibitor of protein synthesis, on facilitation of sexual receptivity in ovariectomized rats. The rats received 0.5 microgram estradiol benzoate (EB), s.c. once daily on days 8 through 12 after ovariectomy (OVX). Either CHX (in 0.5 microliter saline) or 0.5 microliter saline was injected into the lateral septum (LS), cortical nucleus (ACO) or medial nucleus of the amygdala or medial preoptic area on day 11 after OVX. The dose of EB was insufficient to facilitate lordotic behavior on day 10 or day 12 after OVX unless CHX was injected into the LS or ACO. Injection of saline did not influence lordosis.

Animals↗

Age and sex-dependent decreases in ChAT in basal forebrain nuclei.

Microdissection techniques were utilized to measure the activity of choline acetyltransferase (ChAT) (enzyme responsible for synthesis of acetylcholine) in individual basal forebrain nuclei of aged (24 month) and young (4 month) male and female rats. Small but consistent decreases in the activity of ChAT in aged rats were found, and the location of the changes was dependent on the sex of the rat. Aged female rats showed approximately 30% lower ChAT and 40% lower acetylcholinesterase (AChE) activity in the ventral globus pallidus (vGP). Aged males did not show decreased ChAT in the vGP but activity in the medial aspect of the horizontal diagonal band nucleus was 50% lower than in the young males. ChAT activity in four other closely aligned basal forebrain nuclei was not different between the young and aged rats. Analysis of cell number, density and area in the vGP by AChE histochemistry showed no significant differences between aged and young females. In addition, age and sex-dependent changes were measured in pituitary glucose-6-phosphate dehydrogenase activity. The relationship of the changes to age-dependent decrements in memory, the possible influence of gonadal hormones on aging, and the mechanisms responsible for age-related declines in ChAT activity are discussed.

Age Factors↗