This paper presents evidence which demonstrates that a site within the anterior hypothalamus of t... more This paper presents evidence which demonstrates that a site within the anterior hypothalamus of the Syrian hamster is essential for the expression of a photoperiodic response but not for the expression of oestrous or circadian activity rhythms. Selective lesions of the anterior hypothalamic nucleus (AHN) were produced by localized infusions of n-methyl aspartic acid (NMA). Histological analysis revealed that the suprachiasmatic and paraventricular nuclei were resistant to the toxin. Circadian locomotor activity rhythms and oestrous cyclicity were unaffected by these lesions but the photoperiodic response of the gonads to short day length (8L:16D) was completely prevented. In marked contrast to control animals, lesioned animals maintained large testes or ovulatory ovaries, even after 10 weeks of exposure to the inhibitory photoperiod. These data suggest that neurones within the AHN form an essential component of the photoperiod time-measuring apparatus which is independent of that controlling circadian rhythmicity.
This study investigates basal levels of cortisol and dehydroepiandrosterone (DHEA), and their rel... more This study investigates basal levels of cortisol and dehydroepiandrosterone (DHEA), and their relation to gender and pubertal development, in healthy children and adolescents. Salivary cortisol and DHEA levels were examined in 129 normally developing subjects aged eight to 16 years. Subjects provided morning (08:00 h) and evening (20:00 h) saliva samples over four consecutive days. Pubertal stage was assessed using Tanner stage sketches, and subjects were grouped according to their general status of pubertal development (pre-early puberty: Tanner stage<III; mid-post puberty: Tanner stage>II). Results showed that morning salivary cortisol in mid-postpubertal girls was greater than in mid-postpubertal boys, but not pre-early pubertal girls and boys. Mean levels of salivary DHEA were greater in mid-postpubertal boys and girls than in pre-early pubertal boys and girls. Changes in hypothalamic-pituitary-adrenal (HPA) axis function that occur during puberty may have implications for immediate and long-term adolescent health.
Depression (MDD) is prodromal to, and a component of, Alzheimer's disease (AD): it may also b... more Depression (MDD) is prodromal to, and a component of, Alzheimer's disease (AD): it may also be a trigger for incipient AD. MDD is not a unitary disorder, so there may be particular subtypes of early life MDD that pose independent high risks for later AD, though the identification of these subtypes is problematical. There may either be a common pathological event underlying both MDD and AD, or MDD may sensitize the brain to a second event ('hit') that precipitates AD. MDD may also accelerate brain ageing, including altered DNA methylation, increased cortisol but decreasing DHEA and thus the risk for AD. So far, genes predicting AD (e.g. APOEε4) are not risk factors for MDD, and those implicated in MDD (e.g. SLC6A4) are not risks for AD, so a common genetic predisposition looks unlikely. There is as yet no strong indication that an epigenetic event occurs during some forms of MDD that predisposes to later AD, though the evidence is limited. Glucocorticoids (GCs) are distur...
Not for the first time, medicine is beginning to accept what folklore has been saying for some ti... more Not for the first time, medicine is beginning to accept what folklore has been saying for some time-in this case, that stress causes illness. Causation is most comfortably accepted in medicine when it relates to definable physical events: bacteria cause infection, radiation can cause cancer; exposure to toxic chemicals can cause blood abnormalities, and so on, though we know that even these relations are not simple. How can stress cause anything? Method In a cross disciplinary and wide ranging paper such as this, it seems useful to give most references to books or reviews that summarise current evidence or opinion. However, the factual statements are based on the primary literature, which I accessed in the usual way: from personal collections of reprints, from databases (such as BIDS and Medline, using keywords such as "stress" or "depression" coupled with other keywords such as "adrenal steroids," "corticoids," "serotonin," etc), from reviews (some cited in this paper), from scanning key journals, and from contact with colleagues.
Prevention and Control of Aggression and the Impact on its Victims, 2001
... ru Calvo-Torrent, Angels Area of Psychobiology Faculty of Psychology, University of Valencia,... more ... ru Calvo-Torrent, Angels Area of Psychobiology Faculty of Psychology, University of Valencia, Avda. ... E-mail: PPollard@ uclan. ac. uk Pollock, Donna University Institute of Traffic and Road Safety (INTRAS), University of Valencia, C/Hugo de Moncada, 4, 46010 Valencia, Spain. ...
The expression of c-fos protein was examined in the basal forebrains of male rats 60 min followin... more The expression of c-fos protein was examined in the basal forebrains of male rats 60 min following intracerebroventricular infusions of 250 pmol angiotensin II. Levels of corticosterone and vasopressin were also measured at the same time point. In animals not allowed access to water after infusion, angiotensin II induced intense c-fos expression in a band of neurons extending throughout the anterior region of the third ventricle region, including the organum vasculosum of the lamina terminalis, the median preoptic nucleus (nucleus medianus) and the subfornical organ. There were also high levels of expression in the hypothalamic supraoptic nucleus and the paraventricular nucleus, particularly its lateral (magnocellular) region, though other, parvicellular areas were also affected. No other area of the hypothalamus was altered. There was increased c-fos expression in the central nucleus of the amygdala and the bed nucleus of the stria terminalis. Allowing rats to drink during the 60-rain survival period modified this pattern of response, c-fos was markedly reduced in the supraoptic nucleus and the paraventricular nucleus but not in the other areas examined, including the anterior region of the third ventricle and the amygdala. When water was withheld for 15 rain, but then allowed, rats drank the same total volume but c-fos expression was no longer inhibited in either the supraoptic nucleus or paraventricular nucleus. When rats were given 0.9% saline to drink, they ingested about three times as much as water, but angiotensin II-induced c-fos expression was similar to that in rats denied access to water. The pattern was similar following access to 1.8% saline, though levels in the organum vasculosum of the lamina terminalis were reduced. There was a marked correlation between the number of c-fos-positive neurons in the supraoptic nucleus or paraventricular nucleus and plasma levels of corticosterone 60 min after infusion, but not with arginine-vasopressin levels.
THE ovarian hormones of the female rhesus monkey considerably influence sexual behaviour both in ... more THE ovarian hormones of the female rhesus monkey considerably influence sexual behaviour both in free-living groups1 and in experimental situations in the laboratory2,3. There are at least two properties in the female which are concerned in her interaction with the male: first, her sexual attractiveness, and second, her sexual receptivity-the willingness of the female to engage in copulation. These two components have now been found to respond differently to alterations in the female's hormonal state.
Seven castrated monkeys were given either 50 or 100 μg 5α-dihydrotestosterone (DHT) propionate/kg... more Seven castrated monkeys were given either 50 or 100 μg 5α-dihydrotestosterone (DHT) propionate/kg per day. There was no correlation between serum and cerebrospinal fluid (CSF) levels of DHT, which remained very low in the CSF (0·3–0·6% of blood levels) despite the presence of high, supraphysiological amounts in the circulation. There was also no relation between unbound DHT in the blood and the CSF, in which all DHT is unbound. These results differ from previous work on testosterone, the metabolic precursor of DHT. 5α-Dihydrotestosterone propionate at the higher dose maintained suppressed levels of serum LH; LH in two out of four monkeys treated at the lower dose increased to levels observed in castrated, untreated rhesus monkeys. There was no predictable relationship between the amount of DHT in the CSF and levels of LH in the blood: by contrast, DHT in the blood was correlated with serum levels of LH. Levels of LH rose in monkeys in which total blood DHT fell below about 68 nmol/l...
SUMMARY Grooming behaviour was studied quantitatively by observing pairs of oppositely sexed, adu... more SUMMARY Grooming behaviour was studied quantitatively by observing pairs of oppositely sexed, adult rhesus monkeys during regular hourly test sessions over 2 yr.; at all other times the animals were caged singly. Rhythmic fluctuations in both male and female grooming occurred in relation to the menstrual cycle; the grooming times of males reached a maximum near mid-cycle, at which time the females' grooming was at a minimum. In some pairs, there were additional changes in the grooming times immediately before menstruation in the same direction as those near mid-cycle. Bilateral ovariectomy of the female of the pair abolished all rhythmic variations and reduced the grooming of the males. Subcutaneous injections of oestradiol into the ovariectomized female restored the grooming of males to the levels seen near mid-cycle. The subsequent addition of progesterone partially, but always consistently, antagonized the effects of oestradiol. Analysis of the hormone-induced alterations in ...
SUMMARY Male sexual behaviour was studied quantitatively by observing pairs of oppositely sexed, ... more SUMMARY Male sexual behaviour was studied quantitatively by observing pairs of oppositely sexed, adult rhesus monkeys during regular hourly test sessions over 2 yr.; at all other times the animals were housed singly. Rhythmic fluctuations in the mounting behaviour of males occurred in relation to the menstrual cycles of female partners. Two patterns were seen: those with high and low levels of mounting, respectively, in follicular and luteal phases, and those with more isolated maxima near mid-cycle. Ejaculation times were shortest and mounting rates highest near ovulation. Bilateral ovariectomy of females abolished all rhythmic variations in the behaviour of the males, which also stopped ejaculating. Subcutaneous injections of oestradiol into ovariectomized females restored the sexual performance of males, an effect which was partly antagonized by the subsequent addition of progesterone. These findings indicate that sexual behaviour in a male primate is influenced, in some way, by ...
The effect of photoperiodic conditions on sexual behavior was investigated in male Syrian hamster... more The effect of photoperiodic conditions on sexual behavior was investigated in male Syrian hamsters that were either gonadally intact, or castrated and treated with low doses of testosterone throughout the experiment. Hamsters were exposed to long (LD 16:8) or short (LD 8:16) days for 7 weeks; for the next 8 weeks, either they were exposed to an intermediate daylength (LD 12:12), or daylength conditions remained unchanged. Sexual behavior was affected by photoperiod conditions in both gonadally intact animals and testosterone-treated castrates, but to different degrees. Intact males exposed to short days for 15 weeks exhibited gonadal regression, and their copulatory performance was impaired. The percentage of animals that intromitted or ejaculated was significantly reduced. Additional measures of sexual performance among the copulating males were also affected. In contrast, among the castrates with testosterone clamped at low but stable levels, the proportion of males that mounted, intromitted, or ejaculated was not affected by photoperiod. However, among the males that continued to copulate, sexual performance changes were present in the short-day castrates that resembled those displayed by the intact males. We infer that these behavioral effects in both hormonal conditions reflect primarily a difficulty in the attainment of intromission. Gonadal regression alone cannot easily account for the behavioral deficits of the intact males, because circulating testosterone levels at the end of the experiment were not significantly different between the gonadally intact hamsters and the castrated, testosterone-treated hamsters exposed continuously to short days. Males transferred from either long or short days to the intermediate-daylength condition responded behaviorally to this photoperiod as if it were a short day, that is, their ejaculatory frequency declined. We conclude that male hamsters exposed to photoinhibitory daylengths exhibit deficits in their sexual behavior, not only because endogenous levels of testosterone decrease, but also because the substrates on which this hormone acts become less responsive. We hypothesize that under physiological conditions, the episodic secretion of testosterone imposes constraints on the maintenance or restoration of copulation, and that the potent behavioral effects achieved by constant-release implants of testosterone may mask the presence of photoperiodically induced alterations in the hamster's sensitivity to this gonadal hormone.
This paper presents evidence which demonstrates that a site within the anterior hypothalamus of t... more This paper presents evidence which demonstrates that a site within the anterior hypothalamus of the Syrian hamster is essential for the expression of a photoperiodic response but not for the expression of oestrous or circadian activity rhythms. Selective lesions of the anterior hypothalamic nucleus (AHN) were produced by localized infusions of n-methyl aspartic acid (NMA). Histological analysis revealed that the suprachiasmatic and paraventricular nuclei were resistant to the toxin. Circadian locomotor activity rhythms and oestrous cyclicity were unaffected by these lesions but the photoperiodic response of the gonads to short day length (8L:16D) was completely prevented. In marked contrast to control animals, lesioned animals maintained large testes or ovulatory ovaries, even after 10 weeks of exposure to the inhibitory photoperiod. These data suggest that neurones within the AHN form an essential component of the photoperiod time-measuring apparatus which is independent of that controlling circadian rhythmicity.
This study investigates basal levels of cortisol and dehydroepiandrosterone (DHEA), and their rel... more This study investigates basal levels of cortisol and dehydroepiandrosterone (DHEA), and their relation to gender and pubertal development, in healthy children and adolescents. Salivary cortisol and DHEA levels were examined in 129 normally developing subjects aged eight to 16 years. Subjects provided morning (08:00 h) and evening (20:00 h) saliva samples over four consecutive days. Pubertal stage was assessed using Tanner stage sketches, and subjects were grouped according to their general status of pubertal development (pre-early puberty: Tanner stage<III; mid-post puberty: Tanner stage>II). Results showed that morning salivary cortisol in mid-postpubertal girls was greater than in mid-postpubertal boys, but not pre-early pubertal girls and boys. Mean levels of salivary DHEA were greater in mid-postpubertal boys and girls than in pre-early pubertal boys and girls. Changes in hypothalamic-pituitary-adrenal (HPA) axis function that occur during puberty may have implications for immediate and long-term adolescent health.
Depression (MDD) is prodromal to, and a component of, Alzheimer's disease (AD): it may also b... more Depression (MDD) is prodromal to, and a component of, Alzheimer's disease (AD): it may also be a trigger for incipient AD. MDD is not a unitary disorder, so there may be particular subtypes of early life MDD that pose independent high risks for later AD, though the identification of these subtypes is problematical. There may either be a common pathological event underlying both MDD and AD, or MDD may sensitize the brain to a second event ('hit') that precipitates AD. MDD may also accelerate brain ageing, including altered DNA methylation, increased cortisol but decreasing DHEA and thus the risk for AD. So far, genes predicting AD (e.g. APOEε4) are not risk factors for MDD, and those implicated in MDD (e.g. SLC6A4) are not risks for AD, so a common genetic predisposition looks unlikely. There is as yet no strong indication that an epigenetic event occurs during some forms of MDD that predisposes to later AD, though the evidence is limited. Glucocorticoids (GCs) are distur...
Not for the first time, medicine is beginning to accept what folklore has been saying for some ti... more Not for the first time, medicine is beginning to accept what folklore has been saying for some time-in this case, that stress causes illness. Causation is most comfortably accepted in medicine when it relates to definable physical events: bacteria cause infection, radiation can cause cancer; exposure to toxic chemicals can cause blood abnormalities, and so on, though we know that even these relations are not simple. How can stress cause anything? Method In a cross disciplinary and wide ranging paper such as this, it seems useful to give most references to books or reviews that summarise current evidence or opinion. However, the factual statements are based on the primary literature, which I accessed in the usual way: from personal collections of reprints, from databases (such as BIDS and Medline, using keywords such as "stress" or "depression" coupled with other keywords such as "adrenal steroids," "corticoids," "serotonin," etc), from reviews (some cited in this paper), from scanning key journals, and from contact with colleagues.
Prevention and Control of Aggression and the Impact on its Victims, 2001
... ru Calvo-Torrent, Angels Area of Psychobiology Faculty of Psychology, University of Valencia,... more ... ru Calvo-Torrent, Angels Area of Psychobiology Faculty of Psychology, University of Valencia, Avda. ... E-mail: PPollard@ uclan. ac. uk Pollock, Donna University Institute of Traffic and Road Safety (INTRAS), University of Valencia, C/Hugo de Moncada, 4, 46010 Valencia, Spain. ...
The expression of c-fos protein was examined in the basal forebrains of male rats 60 min followin... more The expression of c-fos protein was examined in the basal forebrains of male rats 60 min following intracerebroventricular infusions of 250 pmol angiotensin II. Levels of corticosterone and vasopressin were also measured at the same time point. In animals not allowed access to water after infusion, angiotensin II induced intense c-fos expression in a band of neurons extending throughout the anterior region of the third ventricle region, including the organum vasculosum of the lamina terminalis, the median preoptic nucleus (nucleus medianus) and the subfornical organ. There were also high levels of expression in the hypothalamic supraoptic nucleus and the paraventricular nucleus, particularly its lateral (magnocellular) region, though other, parvicellular areas were also affected. No other area of the hypothalamus was altered. There was increased c-fos expression in the central nucleus of the amygdala and the bed nucleus of the stria terminalis. Allowing rats to drink during the 60-rain survival period modified this pattern of response, c-fos was markedly reduced in the supraoptic nucleus and the paraventricular nucleus but not in the other areas examined, including the anterior region of the third ventricle and the amygdala. When water was withheld for 15 rain, but then allowed, rats drank the same total volume but c-fos expression was no longer inhibited in either the supraoptic nucleus or paraventricular nucleus. When rats were given 0.9% saline to drink, they ingested about three times as much as water, but angiotensin II-induced c-fos expression was similar to that in rats denied access to water. The pattern was similar following access to 1.8% saline, though levels in the organum vasculosum of the lamina terminalis were reduced. There was a marked correlation between the number of c-fos-positive neurons in the supraoptic nucleus or paraventricular nucleus and plasma levels of corticosterone 60 min after infusion, but not with arginine-vasopressin levels.
THE ovarian hormones of the female rhesus monkey considerably influence sexual behaviour both in ... more THE ovarian hormones of the female rhesus monkey considerably influence sexual behaviour both in free-living groups1 and in experimental situations in the laboratory2,3. There are at least two properties in the female which are concerned in her interaction with the male: first, her sexual attractiveness, and second, her sexual receptivity-the willingness of the female to engage in copulation. These two components have now been found to respond differently to alterations in the female's hormonal state.
Seven castrated monkeys were given either 50 or 100 μg 5α-dihydrotestosterone (DHT) propionate/kg... more Seven castrated monkeys were given either 50 or 100 μg 5α-dihydrotestosterone (DHT) propionate/kg per day. There was no correlation between serum and cerebrospinal fluid (CSF) levels of DHT, which remained very low in the CSF (0·3–0·6% of blood levels) despite the presence of high, supraphysiological amounts in the circulation. There was also no relation between unbound DHT in the blood and the CSF, in which all DHT is unbound. These results differ from previous work on testosterone, the metabolic precursor of DHT. 5α-Dihydrotestosterone propionate at the higher dose maintained suppressed levels of serum LH; LH in two out of four monkeys treated at the lower dose increased to levels observed in castrated, untreated rhesus monkeys. There was no predictable relationship between the amount of DHT in the CSF and levels of LH in the blood: by contrast, DHT in the blood was correlated with serum levels of LH. Levels of LH rose in monkeys in which total blood DHT fell below about 68 nmol/l...
SUMMARY Grooming behaviour was studied quantitatively by observing pairs of oppositely sexed, adu... more SUMMARY Grooming behaviour was studied quantitatively by observing pairs of oppositely sexed, adult rhesus monkeys during regular hourly test sessions over 2 yr.; at all other times the animals were caged singly. Rhythmic fluctuations in both male and female grooming occurred in relation to the menstrual cycle; the grooming times of males reached a maximum near mid-cycle, at which time the females' grooming was at a minimum. In some pairs, there were additional changes in the grooming times immediately before menstruation in the same direction as those near mid-cycle. Bilateral ovariectomy of the female of the pair abolished all rhythmic variations and reduced the grooming of the males. Subcutaneous injections of oestradiol into the ovariectomized female restored the grooming of males to the levels seen near mid-cycle. The subsequent addition of progesterone partially, but always consistently, antagonized the effects of oestradiol. Analysis of the hormone-induced alterations in ...
SUMMARY Male sexual behaviour was studied quantitatively by observing pairs of oppositely sexed, ... more SUMMARY Male sexual behaviour was studied quantitatively by observing pairs of oppositely sexed, adult rhesus monkeys during regular hourly test sessions over 2 yr.; at all other times the animals were housed singly. Rhythmic fluctuations in the mounting behaviour of males occurred in relation to the menstrual cycles of female partners. Two patterns were seen: those with high and low levels of mounting, respectively, in follicular and luteal phases, and those with more isolated maxima near mid-cycle. Ejaculation times were shortest and mounting rates highest near ovulation. Bilateral ovariectomy of females abolished all rhythmic variations in the behaviour of the males, which also stopped ejaculating. Subcutaneous injections of oestradiol into ovariectomized females restored the sexual performance of males, an effect which was partly antagonized by the subsequent addition of progesterone. These findings indicate that sexual behaviour in a male primate is influenced, in some way, by ...
The effect of photoperiodic conditions on sexual behavior was investigated in male Syrian hamster... more The effect of photoperiodic conditions on sexual behavior was investigated in male Syrian hamsters that were either gonadally intact, or castrated and treated with low doses of testosterone throughout the experiment. Hamsters were exposed to long (LD 16:8) or short (LD 8:16) days for 7 weeks; for the next 8 weeks, either they were exposed to an intermediate daylength (LD 12:12), or daylength conditions remained unchanged. Sexual behavior was affected by photoperiod conditions in both gonadally intact animals and testosterone-treated castrates, but to different degrees. Intact males exposed to short days for 15 weeks exhibited gonadal regression, and their copulatory performance was impaired. The percentage of animals that intromitted or ejaculated was significantly reduced. Additional measures of sexual performance among the copulating males were also affected. In contrast, among the castrates with testosterone clamped at low but stable levels, the proportion of males that mounted, intromitted, or ejaculated was not affected by photoperiod. However, among the males that continued to copulate, sexual performance changes were present in the short-day castrates that resembled those displayed by the intact males. We infer that these behavioral effects in both hormonal conditions reflect primarily a difficulty in the attainment of intromission. Gonadal regression alone cannot easily account for the behavioral deficits of the intact males, because circulating testosterone levels at the end of the experiment were not significantly different between the gonadally intact hamsters and the castrated, testosterone-treated hamsters exposed continuously to short days. Males transferred from either long or short days to the intermediate-daylength condition responded behaviorally to this photoperiod as if it were a short day, that is, their ejaculatory frequency declined. We conclude that male hamsters exposed to photoinhibitory daylengths exhibit deficits in their sexual behavior, not only because endogenous levels of testosterone decrease, but also because the substrates on which this hormone acts become less responsive. We hypothesize that under physiological conditions, the episodic secretion of testosterone imposes constraints on the maintenance or restoration of copulation, and that the potent behavioral effects achieved by constant-release implants of testosterone may mask the presence of photoperiodically induced alterations in the hamster's sensitivity to this gonadal hormone.
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