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Biomedical subjects

B B Gorzalka

Publications and source records attributed to B B Gorzalka.

At least 19 recordsLinked to original sources

Is there a role for the endocannabinoid system in the etiology and treatment of melancholic depression?

With advances in basic and clinical neuroscience, many gaps have appeared in the traditional monoamine theory of depression that have led to reformulation of the hypotheses concerning the neurobiology of depression. The more recent hypotheses suggest that melancholic depression is characterized by central glucocorticoid resistance that results in hypercortisolemia, which in turn leads to down-regulation of neurotrophins and subsequent neurodegeneration. Examining the neurobiology of depression from this perspective suggests that the endocannabinoid system may play a role in the etiology of melancholic depression. Specifically, pharmacological and genetic blockade of the cannabinoid CB1 receptor induces a phenotypic state that is analogous to melancholic depression, including symptoms such as reduced food intake, heightened anxiety, increased arousal and wakefulness, deficits in extinction of aversive memories and supersensitivity to stress. These similarities between melancholic depression and an endocannabinoid deficiency become more interesting in light of recent findings that endocannabinoid activity is down-regulated by chronic stress and possibly increased by some antidepressant regimens. We propose that an endocannabinoid deficiency may underlie some of the symptoms of melancholic depression, and that enhancement of this system may ultimately be a novel form of pharmacotherapy for treatment-resistant depression.

Animals↗

Melatonin protects against the effects of chronic stress on sexual behaviour in male rats.

The effects of chronic mild stress (CMS) on both sexual behaviour and wet dog shakes (WDS), a serotonergic type 2A (5-HT2A) receptor-mediated behaviour, were explored in the male rat. In addition, the possible attenuation of these effects by chronic treatment with melatonin, a putative 5-HT2A antagonist, was examined. The CMS procedure resulted in a significant increase in WDS and an overall decrease in all aspects of sexual behaviour. Concurrent melatonin administration attenuated the CMS-induced effects on sexual behaviour, but not the effects on either spontaneous WDS or WDS in response to the 5-HT2A agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, suggesting a mechanism of action other than exclusive 5-HT2A antagonism. These results are the first to demonstrate that melatonin significantly protects against the detrimental effects of a chronic stressor on sexual behaviour.

Animals↗

Ketanserin attenuates the behavioural effects of corticosterone: implications for 5-HT(2A) receptor regulation.

The effects of chronic corticosterone treatment on sexual behaviour and wet-dog shakes were investigated in both female and male rats. The serotonergic type 2A (5-HT(2A)) receptor antagonist ketanserin was administered to test the hypothesis that the behavioural effects of corticosterone were mediated by increased 5-HT(2A) receptor activity. Rats were randomly assigned to one of four chronic treatment groups: control, ketanserin alone, corticosterone alone, or ketanserin and corticosterone. Ketanserin attenuated the corticosterone-induced changes in both sexual behaviour and wet-dog shakes. Ketanserin alone had no effect on these behaviours. Results suggest that increased 5-HT(2A) receptor activity mediates the effects of corticosterone on sexual behaviour and wet-dog shakes.

Animals↗

Paradoxical effects of chronic corticosterone on forced swim behaviours in aged male and female rats.

The effects of chronically administered corticosterone on forced swim test and open field test behaviours were explored in aged male and female rats. Though corticosterone has typically been associated with depressive behaviours, recent data have suggested a putative antidepressive effect of corticosterone. The current study used the forced swim test as a model of antidepressant efficacy in order to explore this. Aged male and female rats received either corticosterone (20 mg/kg) or the vehicle for 10 days before testing in the forced swim test, then for an additional 3 days before testing in the open field test. On day 11, each animal was individually tested on the duration of swimming, immobile, and struggling behaviours, and on day 14, for the display of rearing and line crossing behaviours. Results revealed that corticosterone significantly increased swimming and decreased immobility behaviour in females, but failed to do so in males. Additionally, there was a main effect of corticosterone on struggling behaviour such that it decreased it in males. There were no effects of corticosterone or sex on open field test behaviours, suggesting that the present findings are not accounted for by a general effect of corticosterone on motor behaviour. Overall, the data suggest that chronically administered corticosterone possesses effects that are sex-specific, and that it may exert mildly antidepressive effects in females, but the opposite effects in males. These data are consistent with emerging evidence that corticosterone may play a paradoxical antidepressive effect.

Aging↗

Sex differences in forced-swim and open-field test behaviours after chronic administration of melatonin.

The effects of melatonin administered chronically on forced-swim test and open-field test behaviours were examined in male and female rats. The forced-swim test has been shown to be sensitive to all major classes of antidepressants and evidence indicates that melatonin possesses putative antidepressive properties. Male and female Long-Evans rats received either a regimen of chronic administration of melatonin or the control condition for 14 days via the drinking water. On day 15, each animal was individually introduced into a swim chamber, and was scored for 15 min on the duration of swimming, struggling, and immobility. After 24 h, each animal was again tested in the forced-swim test for 10 min. On day 18, all animals were tested in the open-field test apparatus for 5 min. Results revealed that females consistently showed higher activity levels than males in the forced-swim and open-field tests. Melatonin significantly increased struggling in males on day 15, but failed to do so in females. Also, whereas melatonin-treated females showed higher levels of behavioural immobility during their first exposure to the forced-swim test, this effect was prevented upon a second exposure. In both males and females, melatonin decreased swimming in the forced-swim test while increasing open-field ambulatory behaviour. Therefore, it is unlikely that melatonin's mechanism of action is a general inhibitory effect on motor activity. Taken together, the results suggest that the effects of melatonin treatment on forced-swim test behaviours are sex- and test-dependent.

Animals↗

Melatonin enhances sexual behavior in the male rat.

Anecdotal reports suggest that melatonin enhances libido in men. However, controlled trials remain to be published for any species. Accordingly, adult male rats were chronically treated for 12 weeks with melatonin via the drinking water. On the 13th week, all males were tested in the presence of sexually receptive females on measures of sexual behavior. Moreover, because of the established inverse relationship between male sexual behavior and serotonergic type 2A (5-HT(2A)) receptor activity, "wet-dog shakes" (WDS), a 5-HT(2A) receptor mediated behavior, were measured concurrently. All aspects of sexual activity were significantly facilitated in males treated with melatonin. In addition, there was a consistent, progressive reduction in the frequency of WDS, suggestive of a temporal decrement in serotonergic receptor activity and supportive of previous indications that melatonin possesses 5-HT(2A) antagonistic properties. These results provide the first empirical evidence for a facilitatory role of melatonin in sexual behavior, and suggest that its mechanism of action may involve the 5-HT(2A) receptor.

Animals↗

Measurement of some small-molecule and peptide neurotransmitters in-vitro using a fiber-optic probe with pulsed ultraviolet resonance Raman spectroscopy.

Many techniques have been developed to investigate the chemistry associated with brain activity. These techniques generally fall into two categories: fast techniques with species-limited sensitivity; and generally slower techniques with broader species sensitivity. Therefore, a need exists for a fast, minimally invasive technique that is sensitive to a wide array of biologically relevant compounds in order to measure chemical brain events in real time. The work presented here describes the development of a novel spectroscopic neurotransmitter probe for the rapid and simultaneous detection of a variety of neurotransmitters. A fiber-optic-linked Raman and tunable ultraviolet resonance Raman system was assembled with custom designed optical fiber probes. Using this system, the ultraviolet resonance Raman spectra of some small-molecule and peptide neurotransmitters were measured in-vitro with a fiber-optic probe and are reported here for the first time. The probe has furthermore been used to measure neurotransmitter secretions obtained from depolarized rat pheochromocytoma (PC12) cells. These results demonstrate the general utility of this approach which, due to the fiber-optic implementation, could potentially also be applied to in-vivo neurotransmitter determinations.

Acetylcholine↗

Nefazodone attenuates the stress-induced facilitation of wet dog shaking behaviour but not the facilitation of sexual behaviour in female rats.

The effects of chronic stress both alone and in combination with the antidepressant, nefazodone, which possesses antagonistic activity at the 5-HT2A receptor, were examined on the 5-HT2A receptor-mediated behaviour, wet dog shaking and sexual behaviour. Ovariectomized female rats received either a chronic stressor or no stress for 30 days, and half of each group received concurrent nefazodone treatment (100 mg/kg/day). Following treatment with either estrogen, or estrogen combined with progesterone, sexual behaviour and wet dog shaking were recorded. Chronic stress alone was found to facilitate sexual behaviour and increase wet dog shaking, while nefazodone administration alone was without effect. Furthermore, nefazodone completely attenuated the stress-induced facilitation of wet dog shaking, but not sexual behaviour.

Animals↗

Corticosterone regulation of 5-HT2A receptor-mediated behaviors: attenuation by melatonin.

The effects of chronic corticosterone treatment on sexual behavior and on wet-dog shakes (WDS), a serotonergic type 2A (5-HT2A) receptor-mediated behavior, were explored in the male rat. In addition, the effects of acute melatonin treatment, both alone and in combination with corticosterone, were investigated. Chronic injections of corticosterone resulted in an overall decrease in consummatory measures of sexual behavior, and an increase in WDS. Furthermore, although an acute injection of melatonin alone had no effect on any recorded behavior, it attenuated the effects of corticosterone on sexual behavior and WDS. The data suggest that in the context of 5-HT2A receptor-mediated behaviors, melatonin has possible implications as a 5-HT2A antagonist.

Animals↗

The influence of corticosterone on serotonergic stereotypy and sexual behavior in the female rat.

The effects of adrenalectomy and chronic corticosterone treatment on sexual behavior in the ovariectomized female rat were investigated. The serotonergic type 2A (5-HT2A) receptor-mediated behavior 'wet dog shakes' (WDS) was measured concurrently. In Experiment 1, adrenalectomy reduced the frequency of WDS following the administration of the 5-HT(2A/2C) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) but had no effect on spontaneous WDS. In Experiment 2, chronic corticosterone treatment increased DOI-induced WDS in both adrenalectomized and sham-adrenalectomized rats. In Experiment 3, adrenalectomized and sham-adrenalectomized rats were compared on measures of spontaneous WDS and sexual behavior following the administration of estrogen alone, or estrogen in combination with progesterone. Chronic corticosterone and acute progesterone administration increased WDS and facilitated sexual receptivity and proceptivity, while adrenalectomy decreased WDS, facilitated sexual receptivity and inhibited proceptivity. These findings suggest that the behavioral effects seen following hypothalamic-pituitary-adrenal (HPA) axis disruption may, in part, be mediated by altered 5-HT2A receptor responsivity.

Adrenalectomy↗

Effects of housing conditions and 5-HT2A activation on male rat sexual behavior.

Adult male rats were housed individually or in groups for a period of 39 days. In Experiment 1, the effects of housing conditions on sexual behavior and concurrent spontaneous "wet dog shaking" (WDS) were investigated. Individual housing significantly impaired male sexual behavior and resulted in a trend toward increased WDS. In Experiment 2, the effects of housing conditions were examined following administration of the serotonergic type 2A (5-HT2A) agonist DOI. Individual housing significantly increased DOI-induced WDS. The implications of these findings are discussed in the context of stress-induced corticosterone secretion and the possible regulatory effect on 5-HT2A receptors.

Amphetamines↗

The antidepressant, nefazodone, attenuates corticosterone-induced increases in 5-HT2A receptor-mediated behaviors in the female rat.

The effects of chronic corticosterone administration on sexual behavior and on wet-dog shakes, a 5-HT2A mediated behavior, were investigated in the female rat. In addition, effects of the antidepressant nefazodone, a selective 5-HT2A receptor antagonist, both alone and in combination with corticosterone were examined. Testing was conducted in ovariectomized animals primed with estrogen and progesterone. Corticosterone was found to significantly increase sexual receptivity, sexual proceptivity and wet dog shakes. While nefazodone alone had no significant effects, it completely attenuated the corticosterone-induced increases in both sexual behavior and wet dog shakes. This suggests that corticosterone influences sexual behavior and wet dog shakes via a 5-HT2A receptor mechanism.

Animals↗

Chronic stress effects on sexual behavior in male and female rats: mediation by 5-HT2A receptors.

The effects of chronic psychosocial stress on sexual behavior and on the serotonergic type 2A (5-HT2A) receptor-mediated behavior "wet dog shakes" (WDS) were investigated in male and female rats. In Experiment 1, both bilaterally adrenalectomized and sham-adrenalectomized female rats were assigned to either a psychosocial stress condition or a control condition for 62 days. On the 63rd day, estrogen-primed females were compared on measures of sexual behavior and WDS. Immediately after the behavioral tests, the same rats were primed with a subthreshold level of progesterone. Three hours after the administration of progesterone, rats were again scored for sexual behavior and WDS. Psychosocial stress was found to facilitate sexual behavior and increase WDS in sham-adrenalectomized female rats providing they were primed with both estrogen and progesterone. In Experiment 2, intact male rats were assigned to either the psychosocial stress condition or the control condition for 30 days. On the 31st day, males were compared on measures of sexual behavior and WDS. No significant differences were revealed on the spontaneous expression of sexual behavior and WDS. Subsequently, males were retested following the administration of the 5-HT2A agonist, DOI. Psychosocial stress resulted in a significant decrease in male sexual behavior and a concurrent increase in WDS, following the administration of DOI. Taken together, these results suggest that chronic psychosocial stress facilitates female sexual behavior and inhibits male sexual behavior, and that the effects of stress on sexual behavior may be mediated by 5-HT2A receptor activity.

Analysis of Variance↗

Sexual behavior and wet dog shakes in the male rat: regulation by corticosterone.

The potential involvement of adrenal steroids in the regulation of 'wet dog shakes' (WDS) and sexual behavior was investigated in male rats treated or not with the serotonergic type 2A (5-HT2A) agonist DOI (5-HT2A receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane). In Experiment 1, the frequency of both spontaneous and DOI-induced WDS were compared in adrenalectomized and sham-adrenalectomized rats. Adrenalectomy significantly reduced the frequency of DOI-induced WDS. In Experiment 2, adrenalectomized and sham-adrenalectomized rats received either corticosterone or oil chronically and were again scored for WDS behavior. Corticosterone effectively blocked the adrenalectomy-induced reduction of WDS in the DOI treatment condition. In Experiment 3, intact male rats were chronically administered either corticosterone or oil treatment. Animals were then compared on measures of both spontaneous and DOI-induced WDS and sexual behavior. Corticosterone significantly increased WDS and inhibited sexual behavior in both the spontaneous and DOI treatment conditions. These results suggest that the adrenal steroid corticosterone is important in the regulation of WDS and sexual behavior in the male rat and that this regulation may be mediated by activity at 5-HT2A receptors.

Adrenalectomy↗

Amperozide influences feeding independently of 5-HT2A receptor antagonism.

Amperozide has been biochemically classified as a selective 5-HT2A (serotonin type 2A) receptor antagonist. However, research on the behavioral effects of amperozide suggests the possibility of other mechanisms. The present study in the male rat is an investigation of the effect of amperozide on feeding, a behavior which can be inhibited by 5-HT2A agonists such as 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Experiments revealed that amperozide acted to inhibit feeding behavior both when administered alone and when administered in combination with DOI. These results are inconsistent with 5-HT2A receptor antagonism by amperozide. Further experiments suggested that amperozide may be acting via alpha 2-adrenergic or 5-HT1A receptors to inhibit feeding. These studies imply that amperozide's selective 5-HT2A antagonistic activity is behaviorally specific.

Animals↗

beta-endorphin inhibits and facilitates lordosis behaviour in rats depending on ventricular site of administration.

beta-endorphin was administered intracerebroventricularly into the lateral and third ventricles of ovariectomized, oestrogen- and progesterone-primed rats, and its effect on lordosis and ear-wiggling was assessed. A dose of 2 micrograms beta-endorphin facilitated lordosis when infused into the lateral ventricle, but inhibited lordosis when infused into the third ventricle. The effects were the same whether measured at 30, 60 or 90 min following infusion. beta-endorphin had no significant effect on ear-wiggling frequency when administered in either ventricle. The differential effects of beta-endorphin depending on site of administration may reflect the activation of distinct opioid receptor subtypes within the brain.

Analysis of Variance↗

Ethnic and gender differences in sexuality: variations in sexual behavior between Asian and non-Asian university students.

Seven hundred and two (346 non-Asian, 356 Asian) undergraduate volunteers were assessed in a confidential laboratory setting on levels of interpersonal sexual behavior (e.g., petting, intercourse), intrapersonal sexual behavior (e.g., fantasy, masturbation), and sociosexual restrictiveness (e.g., lifetime number of partners, number of "one-night stands"). The purpose was to examine possible differences in sexual behavior between Asian and non-Asian Canadian university students and to determine the association between North American residency and the sexual behavior of Asians. The role of gender on sexual behavior both across and within ethnic groups was also examined. Statistical analyses revealed that Asian students were significantly more conservative than non-Asian students on all measures of interpersonal sexual behavior and sociosexual restrictiveness. Significant differences were also noted between Asian and non-Asian students on most measures of intrapersonal sexual behavior. With the exception of two fantasy items, length of residency in Canada was unrelated to interpersonal sexual behavior, intrapersonal sexual behavior, or sociosexual restrictiveness among Asians. Although gender differences were substantial for intrapersonal sexual behaviors such as fantasy and masturbation, no significant gender differences were found for measures of interpersonal sexual experience, with the exception of reported number of one-night stands.

Acculturation↗

The effects of immediate, delayed, and residual sympathetic activation on sexual arousal in women.

In a recent experiment, Meston and Gorzalka (1995) [Behaviour, Research and Therapy, 33, 651-664] demonstrated a facilitatory effect of sympathetic activation, via acute exercise, on female sexual arousal. The present investigation was designed to examine the time course of this effect. Thirty-six sexually functional women participated in two experimental sessions in which they viewed a neutral film followed by an erotic film. In one of these sessions, Ss were exposed to 20 min of intense exercise (stationary cycling) prior to viewing the films. Subjective (self-report) and physiological (photoplethysmograph) sexual arousal were measured at either 5 min, 15 min, or 30 min post-exercise. Acute exercise marginally decreased vaginal pulse amplitude (VPA) and had no effect on vaginal blood volume (VBV) responses to an erotic film when measured 5 min post-exercise. At 15 min post-exercise, exercise significantly increased VPA and marginally increased VBV responses. At 30 min post-exercise, both VPA and VBV responses to an erotic film were marginally increased. Acute exercise had no significant effect on subjective perceptions of sexual arousal in any of the experimental conditions.

Adolescent↗