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J T Clark

Publications and source records attributed to J T Clark.

54 records · Page 3Linked to original sources

Evidence for the modulation of sexual behavior by alpha-adrenoceptors in male rats.

Clonidine, a commonly used antihypertensive agent believed to act by stimulation of central alpha-adrenoceptors, produced a dose-related suppression of ejaculatory behavior in sexually vigorous male rats throughout the range of treatment (0.0125-0.5 mg/kg). Treatment with 0.25 mg/kg virtually eliminated ejaculatory behavior, without altering the number of animals mounting and intromitting. These effects were maintained for at least 4 h after treatment. Prazosin, another antihypertensive (but acting by blockade of alpha 1-adrenoceptors), increased latencies to initiation of copulation, to ejaculation, and to reinstatement of copulation following ejaculation. Additionally, prazosin (1 mg/kg) pretreatment failed to attenuate or prevent the clonidine-induced suppression of ejaculation. In contrast, yohimbine, a drug which preferentially blocks alpha 2-adrenoceptors (2 mg/kg, 20 min prior to mating tests), caused a facilitation of copulatory behavior as evidenced by drastic decreases in ejaculation latency and intercopulatory and postejaculatory intervals. Pretreatment with yohimbine completely prevented the clonidine-induced suppression of ejaculation, while clonidine attenuated the facilitatory effects of yohimbine, suggesting a competitive interaction. These data lead to the suggestion that increased excitatory adrenergic activity results in increased sexual arousal either by blockade of alpha 2-or stimulation of alpha 1-adrenoceptors. Alternatively, stimulation of alpha 2-or blockade of alpha 1-adrenoceptors results in diminished sexual motivation. While the precise implications of this animal research for the clinic are as yet unclear, further research could lead to important developments in the pharmacological treatment of sexual dysfunctions.

Animals↗

Neuropeptide Y stimulates feeding but inhibits sexual behavior in rats.

The effects of neuropeptide Y (NPY), a tyrosine-rich peptide found in the rat brain, on feeding and sexual behavior were studied in male and female rats. Intraventricular (ivt) injections of NPY during the final hours of the light period induced feeding in a dose-related manner. While the lowest dose tested (0.02 nM) was without effect, higher doses (0.12, 0.47, 2.3 nM) uniformly elicited feeding with a latency of about 15 min in male rats. With the most effective dose, 0.47 nM, the increased food intake was due to an increased local eating rate. In contrast, the pattern of feeding behavior after a related peptide, rat pancreatic polypeptide (rPP), was quite different and less impressive. During the first hour, only one ivt dose of rPP (0.45 nM) evoked an increase in food intake, due to an increased time spent eating. Further, the effects of NPY on food intake were greater during the nocturnal period. Interestingly, increased food intake in nocturnal tests (4 h) was due solely to augmented intake during the first 60 min after ivt administration. In mating tests, initiated 2 h after the onset of darkness and 10 min after ivt administration of peptide, all but the lowest dose of NPY (0.01 nM) drastically suppressed ejaculatory behavior. Most rats treated with higher doses of NPY (0.02, 0.12, or 0.47 nM) mounted and intromitted only a few times before the cessation of sexual activity, and elongated latencies to the initial mount and intromission were observed. In contrast to the dramatic NPY-induced suppression of ejaculatory behavior, rPP (0.11 and 0.45 nM) was without effect on copulatory behavior. To substantiate further that the impairment of sexual behavior seen in NPY-treated rats was not due to an attenuated sexual ability, an additional experiment was performed. Penile reflexes, including erection, were monitored 10 min after ivt injection of NPY (0.12 nM), rPP (0.11 nM), or saline. No effect of NPY or rPP was observed on the proportion of rats showing erection or latency to initial erection, or in the number of erections per test. In fact, a slight facilitation of penile dorsiflexion responses was seen after NPY. These findings suggest that NPY selectively depresses sexual motivation in the male rat. In ovariectomized female rats responding to estrogen plus progesterone with a good level of sexual receptivity (lordosis quotient greater than 70), ivt saline and 0.01 nM NPY were without effect on sexual behavior.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Purchasing medical equipment: a protocol for decision making.

In light of today's tight hospital financial picture caused by Medicare's prospective payment system and local constraints, capital expenditures must be made with great care and forethought. The process for purchase decision making should assess the need for the device; specifically identify what is required; carefully evaluate the product via technical, clinical, and user studies; collate the results for committee decision making; and plan for the introduction and support of the product through its lifetime. A case study of the acquisition of a neonatal monitoring system is presented.

Commerce↗

Enhancement of sexual motivation in male rats by yohimbine.

Yohimbine hydrochloride, an alpha 2-adrenoceptor antagonist, increased sexual motivation in male rats as evidenced by increased mounting performance in mating tests conducted after genital anesthetization, increased percentage of male rats ejaculating in their first heterosexual encounter, and induction of copulatory behavior in sexually inactive male rats. These observations lead to the suggestion that alpha-adrenoceptors are important modulators of sexual arousal in intact male rats. These results indicate that pharmacological treatment of sexual (libido) dysfunction may be useful.

Animals↗

Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats.

Observations that a pancreatic polypeptide-like substance, possibly neuropeptide Y, is present in hypothalamic areas and may coexist with catecholamines prompted evaluation of its role in controlling feeding behavior. Intracerebroventricular administration of 2 or 10 micrograms of human pancreatic polypeptide to ovariectomized rats pretreated with estradiol benzoate plus progesterone significantly increased the number of animals feeding, and total food intake in tests conducted during the light phase of the day. Administration of neuropeptide Y, 2 or 10 micrograms, induced feeding in all rats, and food intake was 3 times greater than that observed after human pancreatic polypeptide injection. These findings imply that neuropeptide Y, or a closely related pancreatic polypeptide-like neuropeptide, plays an important role in neural regulation of feeding behavior.

Animals↗

Further studies on alterations in male rat copulatory behavior induced by the dopamine-receptor agonist RDS-127.

Pharmacologic dopamine receptor stimulation by RDS-127 (2-N,N-di-n-propylamino-4,7-dimethoxyindane) resulted in qualitatively different changes in the mating pattern depending on the dose administered and time elapsed between treatment and behavioral observation. A low dose (0.25 mg/kg) selectively increased the latency to ejaculation whereas a high dose (3.0 mg/kg) decreased ejaculation latency and intromission frequency (both indicators of ejaculatory efficiency) when behavioral observations were begun 30 minutes after intraperitoneal administration. Intermediate doses (0.5, 1.0, and 2.0 mg/kg) did not alter the time required to achieve ejaculation but did lower the number of intromissions preceding ejaculation. These dose-dependent actions resemble the effects of dopaminomimetics (reported by others) on locomotor activity. When mating tests were conducted shortly (less than five minutes) after drug administration, the induction of ejaculation by the high dose was enhanced. At this time, as well as after a prolonged delay (two hours), signs of decreased arousal (longer intromission latencies) were also observed. However, the postejaculatory refractory period was altered in a time-dependent fashion, viz: it was shortened closest to the injection time, not altered 30 minutes after treatment, and increased two hours after RDS-127 administration. Finally, RDS-127 induced seminal emission (ex copula) in 2.9 +/- 0.9 (S.E.) minutes, and these emissions did not differ in weight from normal spontaneous (diurnal) seminal emissions. The RDS-127-induced seminal emission was not followed by a refractory period of similar magnitude to that seen after ejaculation in copula. The data are interpreted in terms of the involvement of dopamine receptor subtypes in the modulation of masculine sexual behavior.

Animals↗

Effects of a potent dopamine receptor agonist, RDS-127, on penile reflexes and seminal emission in intact and spinally transected rats.

Administration of RDS-127 (3.0 mg/kg) induced seminal emission within three minutes of IP injection and suppressed the display of penile reflexes in intact and spinally transected rats. In Experiment 1, RDS-127 was administered to intact, sexually experienced rats in a protocol previously demonstrated to selectively lower the ejaculatory threshold of copulating animals. The incidence of seminal emission was significantly elevated by RDS-127 but penile reflexes were present in only 8% of the drug-treated rats, compared to 59% of controls. In Experiment 2, seminal emission was induced 2.3 +/- 0.4 (S.E.) minutes from injection of RDS-127. Animals which responded to RDS-127 with multiple emissions had significantly lower ejaculation latencies during copulatory tests conducted prior to drug treatment than animals which had no or only single seminal emissions following RDS-127 injection. Spontaneous seminal emission in the 3 day period initiated 2 hours after RDS-127 injection was unaffected by the drug. Spontaneously produced plugs were approximately twice the weight of those induced by RDS-127. In Experiment 3, seminal emission was induced in spinally transected rats 1.7 +/- 0.4 minutes following RDS-127 administration, whereas drug treatment attenuated the enhancement of penile reflexes observed following midthoracic spinal transection. These experiments suggest that a spinally-mediated dopaminergic mechanism is capable of stimulating seminal emission acutely in the rat and inhibiting the display of penile reflexes by the supine animal.

Animals↗

Effects of a novel dopamine-receptor agonist RDS-127 (2-N,N-di-n-propylamino-4,7-dimethoxyindane), on hormone levels and sexual behavior in the male rat.

Selective changes in the mating pattern occurred 30 minutes following administration of RDS-127 (3.0 mg/kg, IP) to sexually experienced adult male rats. Marked decreases in intromission frequency and ejaculation latency were observed. These data indicate a potent effect upon conummatory mechanisms underlying copulatory behavior. The lack of effect upon arousal state was further demonstrated utilizing a "mounting test" (in which the penis is anesthetized by topical application of tetracaine hydrochloride). No difference in mounting behavior was seen. Seminal plugs were noted in a large percentage of treated animals at the time of anesthetic application. Additionally, a six-fold decrease in plasma prolactin and a lesser decrement in plasma luteinizing hormone were evident. Finally, in sexually experienced castrate animals, RDS-127 induced mounting in two thirds and intromissive and ejaculatory patterns in one third of the treated animals, 35 days postcastration. These effects were greatly attenuated by 56 days postcastration. The selective alteration of consummatory mechanisms, with little or no effect upon arousal status, suggests a neurochemical separation of these two components in the intact male rat.

Animals↗

The newborn oxygram: automated processing of transcutaneous oxygen data.

Hypoxemic and hyperoxemic episodes are common in newborns with respiratory disorders. We have developed a microprocessor-based data system for use with transcutaneous oxygen (TcPO2) monitors in an attempt to quantitate these episodes. The amount of time spent by an infant in each of ten preset TcPO2 ranges can be automatically recorded. These data are referred to as the oxygram. Fourteen newborn infants were monitored for a total of 552 hours using this system. They spent a mean of 2.96% of the time with a TcPO2 less than or equal to 40 torr and 0.26% of the time with a TcPO2 greater than 100 torr. Representative oxygrams are presented. Clinical and research applications of the data system are discussed.

Humans↗

The inhibition of sexual behavior in male rats by propranolol is stereoselective.

We have previously reported that administration of racemic mixtures of propranolol was associated with a marked inhibition of mating behavior in male rats. To compare the effects of (+)-propranolol, (-)-propranolol, and (+/-)-propranolol in sexually experienced males, rats ejaculating in four or more mating tests were divided into three groups (N = 16 per group) such that no differences in parameters of copulatory behavior were evidence in preexperimental tests. No major effect of propranolol on parameters of behavior associated with initiation of sexual behavior was evident. In contrast, other measures of behavior were profoundly modified. The ejaculatory threshold, indicated by the number of intromissions preceding ejaculation, was increased after (+)- and (+/-)-propranolol, but not (-)-propranolol. The number of mounts without intromission preceding ejaculation was increased only after (+/-)-propranolol. A decrease in copulatory efficacy was evident after (-)- or (+/-)-propranolol, but not after (+)-propranolol. Increases in ejaculation latency, intercopulatory interval, and postejaculatory interval were observed after (-)- and (+/-)-propranolol, but not after (+)-propranolol. In summary, the present data indicate that the (-) isomer of propranolol is the active form necessary for the inhibitory effects of propranolol on male sexual function. We suggest that this inhibition is due to specific receptor-mediated mechanisms, involving beta-adrenoceptors and 5-HT1A receptor interactions.

Animals↗

Effects of apomorphine on sexual behavior in young and middle-aged rats.

Apomorphine (APO), the prototypical dopamine agonist, produced different effects on the copulatory patterns of sexually vigorous male rats depending on the dose, the time between treatment and behavioral observation and the age of the animals. Prior to any drug treatment, middle-aged males (13 months of age) exhibited prolonged latencies to ejaculation and intervals between intromissions when compared to young male rats (3 months of age). In mating tests to young male rats initiated six minutes after treatment, administration of low doses of APO was followed by reductions in the ejaculatory threshold (0.05-0.8 mg/kg). The greatest reduction in the ejaculatory threshold was observed after administration of 0.4 mg/kg APO. No such facilitation of ejaculatory behavior was evident in the middle-aged males. Age-related differences in APO-induced changes in ejaculation latency (0.05-0.8 mg/kg), intromission frequency (0.05-0.4 mg/kg), copulatory efficacy (0.2 and 0.8 mg/kg) and intercopulatory interval (0.8 mg/kg) were evident. Doses of APO above 0.4 mg/kg in young males and above 0.2 mg/kg in middle-aged males elicited dose-related decreases in the number of rats engaging in copulatory activity, with 3 mg/kg effecting a virtual elimination in both age groups. In mating tests initiated 60 minutes after treatment, no decrease in the number of rats engaging in copulatory activity was seen in the young animals, and 3 mg/kg caused only a minor reduction in the number of middle-aged males achieving ejaculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Aging-induced decrements in neuropeptide Y: the retention of ejaculatory behavior is associated with site-selective differences.

Neuropeptide Y (NPY) has been implicated in the control of reproductive and cardiovascular function. We observed an age-related decrease in the number of males copulating to ejaculation and a moderate systolic hypertension in middle-aged (16- to 17-month-old) rats. NPY content was examined in microdissected brain nuclei in 5 groups of rats: 2 groups of young rats, 1 heterosexually naive and the other ejaculating in 3 successive mating test; 3 groups of middle-aged rats, 1 heterosexually naive, 1 group that had extensive sexual experience but failed to ejaculate in tests at 16.5 months of age, and the third continuing to ejaculate at 16.5 months of age. NPY levels were found to vary depending on the brain area, the age of the animals, and the maintenance of ejaculatory behavior. In sexually naive middle-aged males, NPY levels were uniformly lower than in younger males. There were no differences in NPY levels of young animals, regardless of sexual experience. In the medial preoptic area, the group that retained ejaculatory behavior through 16.5 months of age, had higher levels of NPY than those observed in young sexually experienced rats. In sexually experienced rats that were no longer ejaculating at 16.5 months of age levels were lower than all other groups except the sexually naive middle-aged group. In the hypothalamic arcuate nucleus, levels were equivalent in the young groups and in the middle-aged rats that retained ejaculatory behavior, being greater than in the middle-aged rats that were no longer ejaculating or were sexually naive.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Chronic ethanol ingestion alters parameters of mid-latency auditory evoked potentials in male rats.

The purpose of this study was to determine the effects of chronic ethanol ingestion on components of mid-latency auditory evoked potentials (MAEPs). Male Sprague-Dawley rats were administered 10% ethanol in drinking water for 10 months. MAEPs were obtained and compared to age-matched controls provided tap water. Data were obtained for varying frequencies (4, 8, 16, 24, and 32 kHz) and intensities (65, 75, and 85 dB sound pressure level). Ethanol treatment was associated with increased latencies, as well as decreased amplitudes of Na and Pa. The effects were most prominent for MAEP component Pa, but also appear for component Na. We suggest that chronic alcohol consumption induces structural and/or neurochemical alterations in substrates for cortical information processing.

Acoustic Stimulation↗