(+/-)3,4-Methylenedioxymethamphetamine (MDMA) produces long-term reductions in brain 5-hydroxytryptamine in rats.

(+/-)3,4-Methylenedioxymethamphetamine (MDMA) was administered to rats as a single 40 mg/kg injection s.c. or 40 mg/kg s.c. every second day for 4 injections. Sixteen days following the last injection rats were killed. MDMA produced significant depletions of 5-HT and its metabolite 5-HIAA in the hippocampus and the frontal cortex. 5-HT was depleted to 30% of control value in the hippocampus following a single dose. 5-HT levels were not affected in the hypothalamus, suggesting differential effects on brain 5-HT systems. DA levels in the hypothalamus were significantly increased while NE levels in the frontal cortex were decreased to 73% of control following 4 doses of MDMA. MDMA, therefore, produces long-term depletions in 5-HT which suggests that it may act as a neurotoxin at 5-HT neurons in the brain of rats.

Neuroendocrine, biogenic amine and behavioral responsiveness to a repeated foot-shock-induced analgesia (FSIA) stressor in Sprague-Dawley (CD) and Fischer-344 (CDF) rats.

The neurobehavioral responsiveness of two strains of rats, Fischer-344 (CDF) and Sprague-Dawley (CD), to a repeated foot-shock-induced analgesia (FSIA) stress was compared in this study. Rats were either restrained or freely moving during shock presentation (sham controls were exposed to the shock environment only). The foot-shock (15-s, 1.5-mA scrambled electric shock) was observed to induce analgesia in the CDF, but not the CD strain following acute presentation; analgesia was evaluated using time for tail-withdrawal from hot water (55 degrees C). Both strains exhibited an analgesic response when latency to tail withdrawal was evaluated just prior to daily FSIA presentations over 15 total sessions indicating that these rat strains were behaviorally conditioned to this repeated stressor. However, the levels of conditioned analgesic responses to foot-shock were: greater in the CDF and most evident when rats were restrained on the shock-grid while being administered the foot-shock. All rats were quickly sacrificed following the 15th conditioning session to determine the effects of this stressor on neurotransmitter and neuroendocrine function in both strains of rat. Experimental subjects were exposed to the shock grid but not shocked during this last session. The following was found: plasma corticosterone (CORT) and prolactin levels and adrenal CORT levels were significantly increased by repeated stress in the CDF strain; only plasma CORT levels were elevated in the CD rat; pituitary immunoreactive beta-endorphin levels were significantly higher (+46%) amongst all experimental groups in the CDF strain, but stress was not observed to alter peptide steady-state levels in either strain; dopamine (DA), 5-hydroxytryptamine and metabolites (5-hydroxyindoleacetic acid and dihydroxyphenylacetic acid) levels were generally higher in the hypothalamus and frontal cortex of the CDF rat but turnover rates (implied from metabolite/amine ratios) indicated that these systems were more sluggish in this rat strain; hypothalamic DA turnover was significantly attenuated by repeated FSIA + restraint in both strains, but the dynamics of this effect appeared to be different between rat strains; and frontal cortex 5-HT turnover was significantly elevated by repeated FSIA + restraint in only the CDF rat. This research indicates that the CDF rat is extremely sensitive to an acute FSIA stress and it is less able than the CD rat to adapt to repeated presentation of this stress.

The role of serotonergic neurons in dorsal raphe, median raphe and anterior hypothalamic pressor mechanisms.

The role of serotonergic neurons in the dorsal raphe and median raphe in the pressor response to electrical stimulation of these areas, and the contribution of these neurons to the pressor response to serotonin (5-HT) in the anterior hypothalamus-preoptic area (AH/PO) have been studied by the use of local injections of 5,7-dihydroxytryptamine (5,7-DHT), a neurotoxin selective for 5-hydroxytryptamine (5-HT). When blood pressure was recorded in urethane-anesthetized rats, selective lesions of 5-HT-containing neurons in the dorsal raphe nucleus reduced by 60% the pressor response to electrical stimulation (50 Hz, 100-150 microA, 0.3 msec pulse duration) of this nucleus. On the other hand, selective lesion of 5-HT-containing neurons in the median raphe nucleus had no effect on the pressor response to electrical stimulation of this area. Injection of 5,7-dihydroxytryptamine into the anterior hypothalamus/preoptic area resulted in an increased pressor response to the injection of 5-HT (5 nmol) into the lesioned area 10 days later. Furthermore, the destruction of 5-HT-containing neurons in the dorsal raphe nucleus resulted in an enhanced pressor response to the injection of 5-HT (5 nmol) into the anterior hypothalamus/preoptic area, while the destruction of 5-HT-containing neurons in the median raphe nucleus had no effect on the pressor response to the injection of 5-HT (5 nmol) into the anterior hypothalamus/preoptic area. Therefore, it appears that 5-HT neurons in the dorsal raphe nucleus are important in the pressor response to electrical stimulation and are involved in a pressor mechanism in the anterior hypothalamus/preoptic area.(ABSTRACT TRUNCATED AT 250 WORDS)

Serotonergic-cholinergic interactions in blood pressure control in the rat.

Both serotonergic and cholinergic mechanisms in the hypothalamus are involved in blood pressure control. Because lesion of the dorsal raphe or median raphe nucleus decreases the turnover of hypothalamic acetylcholine, interactions between serotonin and acetylcholine have been investigated in the hypothalamus with respect to blood pressure. Pharmacological manipulations that interfere with cholinergic neurotransmission in the posterior hypothalamus block the pressor response to serotonin in the anterior hypothalamic/preoptic area (AH/PO), reduce the pressor response to dorsal raphe stimulation, and have no effect on the pressor response to median raphe stimulation. Administration of the serotonin antagonist metergoline into the AH/PO blocks the pressor response to serotonin, slightly reduces the response to dorsal raphe stimulation, and does not affect the pressor response to median raphe stimulation. It is concluded that a hypothalamic cholinergic mechanism is needed to enable hypothalamic serotonergic neurons to elevate blood pressure. The dorsal raphe nucleus may be a source of these serotonergic terminals involved in this pressor response.

Interaction of the median raphe nucleus and hypothalamic serotonin with cholinergic agents and pressor responses in the rat.

Experiments were performed to determine whether the pathway by which median raphe stimulation increases blood pressore involves serotonergic terminals in the anterior hypothalamic/preoptic area and cholinergic terminals in the posterior hypothalamus. Injection of 5,7-dihydroxytryptamine into the median raphe nucleus decreases serotonin and turnover of acetylcholine in the hypothalamus of the rat. The hypertensive action of injection of serotonin into the anterior hypothalamic/preoptic area is blocked by injection of atropine or hemicholinium-3 into the posterior hypothalamus and by i.c.v. injection of hemicholinium-3 when measured in urethane-anesthetized rats. However, the pressor effect of electrical stimulation of the median raphe nucleus is not blocked by the intrahypothalamic injection of atropine or hemicholinium-3, only partially blocked by i.c.v. hemicholinium-3 and not blocked by specific lesioning with 5,7-dihydroxytryptamine. Moreover, injection of metergoline into the anterior hypothalamic/preoptic area blocks the pressur response to hypothalamic serotonin but does not block the pressor response to median raphe stimulation. Stimulation of the median raphe nucleus does not affect acetylcholine turnover in the hypothalamus. These results suggest that serotonergic mechanisms in the anterior hypothalamic/preoptic area exert their pressor effect through a pathway with a cholinergic link in the posterior hypothalamus. Serotonergic neurons arising in the median raphe nucleus probably are not involved in this pathway through the hypothalamus, although a cholinergic pathway may be involved elsewhere in their pressor actions. The effect of median raphe nucleus lesion on turnover of acetylcholine in the hypothalamus is most likely unrelated to regulation of blood pressure.

Attendance at a breast screening clinic: a problem of administration or attitudes.

In a study of why a sample of women, aged 45-64 and registered with a group practice in Edinburgh, attended or did not attend the Edinburgh Breast Screening Clinic demographic, aetiological, social, and perceptual characteristics of attenders and non-attenders were compared. Similar proportions of attenders and non-attenders knew the chance of a breast lump being cancer and were aware of the benefits of early diagnosis and treatment. The study, however, suggests that non-attenders saw the screening clinic as a place of risk while the attenders saw screening in a positive light: 79% of non-attenders as compared with 36% of attenders said that they were afraid of cancer being found, and most women attended either to reassure themselves that they had not got breast cancer or to receive early treatment if they had. Furthermore, 72% of non-attenders as compared with 13% of attenders were anxious that their lives would be disrupted if cancer were found at the screening clinic. There may well be an important irreducible element to non-attendance due to attitudinal factors; the ethical implications of attempting to eliminate this require careful consideration.