Red/Green color opponency at detection threshold.

By means of visual stimnulus without temporal or spatial edges, we have achieved better isolation of chromatic signals at detection threshold than has been reported previously. Under various states of adaptation, the spectral sensitivity of the chromatic mechanism detecting middle- and long-wavelength lights corresponds with that deduced from suprathreshold red/green hue equilibriums.

Anosmia in male rhesus monkeys does not alter copulatory activity with cycling females.

Three adult male rhesus monkeys were tested daily with intact adult female partners over the course of four or five mentstrual cycles. The males were made permanently anosmic by chemical ablation of the olfactory epithelium after the second or fourth cycle was completed. All males continued to display typical cycles of copulation with their partners after the anosmia procedures, with the shortest latencies to ejaculation occurring during the periovulatory phase of the partner's ovulatory cycle. Hence, female attractivity and cyclic copulatory performance of rhesus monkeys are not dependent upon olfactory signals.

Regulation of hypothalamic proopiomelanocortin mRNA by leptin in ob/ob mice.

The hormone leptin acts on the brain to regulate feeding, metabolism, and reproduction; however, its cellular targets and molecular mechanisms of action remain to be fully elucidated. The melanocortins, which are derived from the precursor proopiomelanocortin (POMC), are also implicated in the physiological regulation of body weight. POMC-containing neurons express the leptin receptor, and thus it is conceivable that the POMC gene itself may be part of the signaling pathway involved in leptin's action on the brain. Using in situ hybridization and computerized image analysis, we tested the hypothesis that the POMC gene is a target for regulation by leptin by comparing cellular levels of POMC mRNA in the hypothalamus among groups of leptin-deficient (ob/ob) mice, leptin-treated ob/ob mice, and wild-type controls. POMC mRNA levels were significantly reduced throughout the arcuate nucleus in vehicle-treated ob/ob mice relative to wild-type controls, whereas POMC mRNA levels in leptin-treated ob/ob mice were indistinguishable from wild-type controls. These observations suggest that one or more products of POMC serve as an integrative link between leptin and the central mechanisms governing body weight regulation and reproduction.

Leptin is a metabolic gate for the onset of puberty in the female rat.

The timing of puberty onset in mammals is tightly coupled to the animal's nutritional and metabolic state. We conducted two experiments to test the hypothesis that leptin acts as a metabolic signal for the onset of puberty. In the first experiment, we administered leptin (6.3 micrograms/g twice daily) to a group of normal prepubertal female rats and compared their rate of sexual maturation to that of two control groups. The group of leptin-treated animals and one group of control animals were allowed to eat ad lib, while the other group of control animals was pair-fed to the leptin-treated group. Food intake in the leptin-treated group was reduced to approximately 80% of the ad lib-fed control group, resulting in retarded growth in both leptin-treated and pair-fed animals. All measured indices of pubertal maturation-age at vaginal opening, age at first estrus, ovarian weight, ovulatory index (corpora lutea/ovarian section), uterine weight, and uterine cross-sectional area-were significantly delayed in the pair-fed group but not different between the leptin-treated group and ad lib-fed controls. The second experiment was similar to the first, except that both the leptin-treated group and the pair-fed group were fed at 70% of the ad lib-fed controls. Under these conditions, leptin only partially reversed the delay in sexual maturation, as reflected by the age at vaginal opening and first estrus. These results suggest that leptin is not the primary signal that initiates the onset of puberty but that instead, it acts in a permissive fashion, as a metabolic gate, to allow pubertal maturation to proceed-if and when metabolic resources are deemed adequate; moreover, these observations suggest that other metabolic factors, besides leptin, influence the timing of puberty onset under conditions of more severe dietary stress.

Gamma-vinyl-GABA treatment of tardive dyskinesia and other movement disorders.

We conducted a single-blind trial of gamma-vinyl-GABA (GVG) in nine patients: seven with tardive dyskinesia, one with Meige syndrome, and one with Tourette syndrome. Five tardive dyskinesia patients completed the entire 11-week study and, as a group, demonstrated significant decreases in dyskinesia scores. Four of these five tardive dyskinesia patients showed clinically evident improvement, with approximately 30% reduction in dyskinetic symptoms. Other patients had no clinical benefit from GVG. Three patients had transient exacerbation of psychiatric symptoms after sudden withdrawal of GVG, and one patient experienced dose-related confusional episodes. Our results suggest that GABAergic drugs may have a role in treating patients with tardive dyskinesia.

Age-related deficits in brain androgen binding and metabolism, testosterone, and sexual behavior of male rats.

Brain androgen binding and metabolism, serum testosterone (T), and sexual behavior were measured in old and young male Fischer 344 rats. After completion of sexual behavior tests, blood was collected for T assay and brains were removed for simultaneous measurements of cytosolic (ARc) and nuclear (ARn) androgen receptors and aromatase activity (AA) in the preoptic area (POA), hypothalamus (HYP) and amygdala (AMG). In Experiment 1, old and young intact males were examined. None of the old males ejaculated in any of the tests of sexual behavior whereas all of the young males ejaculated. The old males had lower levels of serum T, lower levels of ARn in the POA and HYP and lower levels of AA in the POA. The ARc levels of the old and young males did not differ. Experiment 2 was designed to determine if the deficits in brain androgen binding and metabolism were due to low levels of T. Old and young T-treated gonadectomized (GX-T) males and young intact (I) males were examined. T levels were comparable in the young and old GX-T males and were higher in each of these groups than in the young I males. In sexual behavior tests, all of the young but only 25% of the old GX-T males ejaculated. Although ARn levels in the old GX-T males were lower than in the young GX-T males, they were comparable to the young I male levels. No age-related differences in T induction of AA were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Case report of tardive dyskinesia and parkinsonism associated with amoxapine therapy.

The authors describe a case of tardive dyskinesia and parkinsonism associated with amoxapine. Patients who develop acute parkinsonism while taking amoxapine may be at higher risk for tardive dyskinesia. The authors recommend that amoxapine be prescribed as carefully as other neuroleptics.

Effects of estrogen on the number of neurons expressing beta-endorphin in the medial basal hypothalamus of the female guinea pig.

The distribution pattern of immunoreactive beta-endorphin neurons was studied in female guinea pigs that were ovariectomized, and one week later were injected with 25 micrograms estradiol benzoate or oil. The animals (5 from each group) were perfused after 24 hours with 4% paraformaldehyde. The locations of beta-endorphin cells and fibers were determined using avidin-biotin immunohistochemistry on free-floating vibratome sections. beta-endorphin-immunoreactive fibers were distributed widely throughout specific regions of the rostral forebrain, similar to what has been described in other species. beta-endorphin cell bodies were found in the arcuate nucleus and in adjacent ventrolateral areas throughout the rostrocaudal extent of the basal hypothalamus. Cells immunoreactive to beta-endorphin were also present in the caudal part of the ventromedial nucleus of the hypothalamus. The number of beta-endorphin neurons was quantified in anatomically matched sections through the rostral, medial and caudal basal hypothalamus of estradiol benzoate- and oil-treated guinea pigs. Analysis of variance revealed that the number of immunoreactive beta-endorphin cells was significantly increased in all regions of the basal hypothalamus of estrogen-treated guinea pigs as compared to vehicle-treated animals (P < 0.01). These data indicate that in the guinea pig, the number of neurons expressing beta-endorphin is increased in the arcuate nucleus 24 hours after estrogen treatment.

Idazoxan decreases estrogen-induced lordosis in female but not "hormone-independent" lordosis in male guinea pigs of an inbred strain.

This experiment examined whether the imidazoline idazoxan (which binds to alpha-noradrenergic receptors and to imidazoline-preferring sites) interferes with hormone-dependent or hormone-independent lordosis responses. Ovariectomized (ovx) Strain 2 female guinea pigs which were sexually receptive after receiving estradiol benzoate (EB; 3 micrograms/d for 3 days) were injected with either idazoxan (10 mg/kg) or with vehicle at 24 hr after the last EB injection. Idazoxan significantly decreased EB-facilitated lordosis responses in these females. Castrated Strain 2 males, which show lordosis behavior without gonadal hormone administration, were injected with the same dosage of idazoxan (10 mg/kg) or with vehicle. Idazoxan did not inhibit lordosis behavior in these males.

Age-related deficits in brain estrogen receptors and sexual behavior of male rats.

Neural estrogen receptors (ER), serum testosterone (T), estradiol (E2) and luteinizing hormone (LH), and masculine sexual behavior were measured in young (5 months) and old (24 1/2 months) Fischer 344 male rats. We found that old intact males, which displayed significantly lower levels of sexual behavior, T, and LH than young intact males, also had lower levels of nuclear ER (ERn) in the amygdala (AMG). The age difference in ER binding did not appear to be a consequence of altered blood E2 levels because circulating E2 did not differ between the two age groups. Gonadectomy eliminated ejaculatory behavior and significantly reduced ERn in young males. When we administered exogenous T to gonadectomized males in doses that approximated levels found in young intact males, we found that sexual performance of old males was stimulated to precastration levels but not to levels found in young males. Moreover, such treatment failed to increase ERn in the AMG of old males to the levels measured in the AMG of young males. These results suggest that there is an association between the inability of T to increase ERn concentration in the AMG and the deficits in sexual performance that are characteristic of old males. Thus, the capacity of neural tissue to bind estrogen, presumably derived from circulating T, may be a limiting factor in the determination of androgen responsiveness in aging males.

Cytosol androgen receptors in guinea pig brain and pituitary.

Cytosol androgen receptors were assayed in guinea pig brain and pituitary tissues, using [3H]R1881 as ligand. These receptors had an apparent Kd of 0.04 nM and were androgen-specific (R1881 greater than dihydrotestosterone greater than testosterone = estradiol greater than progesterone). Concentrations of cytosol androgen receptors in castrated adult male guinea pigs were 12.2, 11.6, 6.9, 2.6 and 1.3 fmol per mg protein in anterior pituitary, hypothalamus, medial preoptic area, amygdala and cortex, respectively. No significant differences in receptor levels were observed between castrated adult males and females. The concentration of androgen receptors was significantly lower in the hypothalamus, medial preoptic area and anterior pituitary of castrated neonatal males than in castrated adult male guinea pigs. The systemic injection of the alpha 1-adrenergic antagonist, prazosin, had no significant influence on androgen receptor levels in castrated males in any brain area.

Effects of hypothalamic serotonin depletion on lordosis behavior and gonadal hormone receptors.

The effects of chronic depletion of serotonin on feminine sexual behavior (lordosis), cytosolic progestin receptors and estradiol nuclear receptors were investigated. Intrahypothalamic administration of 5,7-dihydroxytryptamine (5,7-DHT) markedly enhanced lordotic responding in estradiol benzoate (EB)-primed, 5,7-DHT-treated female rats and in EB-progesterone primed, 5,7-DHT-treated male rats. Cytosolic progestin receptors were measured in preoptic-hypothalamic nuclei related to reproductive function in sham and 5,7-DHT-treated rats after EB priming. In both sexes, no differences between sham and 5,7-DHT-treated subjects were noted for progestin binding in the medial preoptic nucleus, ventromedial nucleus or arcuate-median eminence area. Estrogen-nuclear complexes were measured in the same brain nuclei of female rats following EB priming, and no differences between sham and 5,7-DHT-treated rats were found. Under the conditions employed, it would appear that, despite marked elevations in lordotic responsivity, the accumulation of estrogen nuclear receptors and the levels of estrogen inducible progestin receptors remain unaltered after chronic depletion of serotonin. Thus, serotonergic influences on lordosis do not appear to involve changes in the expression of steroid receptor levels in preoptic-hypothalamic nuclei known to mediate hormone-dependent neuroendocrine processes.

Noradrenergic modulation of hypothalamic progestin receptors in female guinea pigs is specific to the ventromedial nucleus.

The concentration of estrogen-induced cytosolic progestin receptors (CPRs) in the hypothalamus of alpha 1-noradrenergic antagonist-treated female guinea pigs is reduced relative to non-drug-treated controls. The present study determined where within the hypothalamus this reduction occurs. Ovariectomized, estradiol-treated guinea pigs were given either the alpha 1-noradrenergic antagonist prazosin or vehicle. Microdissected brain regions were assayed for CPR levels. Prazosin caused a selective relative decrease in CPR levels of the ventromedial nucleus of the hypothalamus. No significant effects of prazosin were seen in other hypothalamic or preoptic area nuclei.

Sex differences in cytosolic progestin receptors in microdissected regions of the hypothalamus/preoptic area of guinea pigs.

Cytosolic progestin receptors (CPRs) were measured in microdissected nuclei of the hypothalamus and preoptic area of male and female guinea pigs. Adult gonadectomized animals were given 3 daily injections of 20 micrograms/day estradiol benzoate (EB) or oil vehicle. 24 h later, animals were sacrificed and cytosolic progestin receptors were measured using the synthetic progestin 3H-R5020. CPR levels did not differ significantly between oil treated males and oil treated females in any brain areas examined. With EB treatment, males showed significant increases in CPRs in most of the brain areas in which females showed increases, i.e. in the medial preoptic area, the periventricular part of the preoptic area, the periventricular part of the anterior hypothalamus, the ventromedial nucleus of the hypothalamus, the periventricular part of the medial hypothalamus and the arcuate-median eminence. However, EB treated males showed significantly lower CPR levels than EB treated females in both the periventricular part of the preoptic area and the periventricular part of the medial hypothalamus.

Monochromatism determined at a long-wavelength/middle-wavelength cone-antagonistic locus.

The foveal increment threshold spectral sensitivity function for a 500 msec raised cosine stimulus without spatial edges exhibits a sharp drop or "notch" in sensitivity that coincides with the wavelength of a long-wavelength adapting field. An appropriate name for this phenomenon is the "Sloan notch", after Louise Sloan, who first observed a notch in a foveal threshold spectrum. We have examined suprathreshold discriminability on both sides of the Sloan notch produced by a 6700 td, 578 nm adapting field. In a temporal two-alternative forced-choice paradigm, a suprathreshold 650 nm low-frequency "standard" stimulus was paired with low-frequency "test" stimuli, of wavelength between 600 and 670 nm and varied intensity; the observer's task was to identify the interval containing the standard. Discriminability of the test and standard typically dropped to chance for some particular test intensity, producing "indiscriminability action spectra", up to 0.7 log units above threshold. Truncated spectra (between about 530 and 560 nm) were also obtained from observers on the middle wavelength side of the Sloan notch, for a 550 nm standard. The indiscriminability action spectra of each observer were identical, up to scaling, with the observer's threshold action spectrum. Analysis of the action spectra shows that the indiscriminable stimuli are rendered equivalent at the input to a neural pathway where L- and M-cone signals converge with opposite sign. We also investigated discriminability in the spectral region containing and immediately surrounding the Sloan notch. Suprathreshold stimuli in the spectral region near the notch produce percepts that are always discriminable from 650 and 550 nm standards (and from one another), and thus we conclude that in this spectral region, perception is mediated in part by a pathway distinct from that which signals the standards. The action spectrum of this latter pathway was estimated with a variant of the discrimination procedure, and found similar to V lambda over the spectral region 575-610 nm.

Cone antagonism along visual pathways of red/green dichromats.

We have measured thresholds for bichromatic test-mixtures in red/green dichromats. Our results provide strong evidence for cone-antagonistic coding along the dichromats' detecting pathways. The threshold behavior of the isolated dichromatic pathways is consistent with that predicted by Opponent Colors Theory. We compare these threshold data with the dichromats' judgments of "blue/yellow" hue equilibria, which we obtained in supra-threshold color-cancellation experiments. The results are consistent with the hypothesis that both sets of data are mediated by the same dichromatic cone antagonistic pathway.

Effects of prenatal antiandrogen treatment on masculinization and defeminization of guinea pigs.

Gonadectomized (gdx) guinea pigs which had received the antiandrogen flutamide prenatally were tested for female-typical and male-typical sexual behavior in adulthood. In tests for lordosis behavior, gdx males and females were injected with estradiol benzoate and progesterone. Prenatally flutamide-treated females showed a longer mean lordosis response than control females. This was true whether they were given either a high or a low dose of EB. No male ever showed a lordosis response. In tests for male-typical sexual behavior, gdx adult males were treated with testosterone propionate and tested with stimulus females. The prenatally flutamide-treated males showed significantly decreased levels of ejaculation, a lower intromission rate and a decreased percentage of mounts which included pelvic thrusts, when compared to control males. Mount rate and rate of pericopulatory behavior did not differ between the flutamide and control males. The fact that prenatal administration of flutamide increased female-typical behavior in adult females suggests that the female guinea pig is normally partially defeminized by androgens in utero. The male guinea pig appears to be resilient to attempts to block defeminization with prenatal antiandrogens. However, some aspects of masculinization can be blocked.

Lordosis behavior in males of two inbred strains of guinea pig.

The lordosis behavior of male guinea pigs from inbred strains 2 and 13 was examined. Significantly more isolated gonadally intact males of strain 2 than strain 13 displayed lordosis. Castration did not decrease the display of lordosis. In castrated strain 2 males, those which showed lordosis did not have higher plasma androgen, estrone or estradiol levels than those which did not show lordosis. They also did not differ hormonally from ovariectomized strain 2 females even though strain 2 females never showed lordosis without hormone replacement. Although the lordosis shown by strain 2 males was not related to endogenous gonadal hormone levels, estradiol benzoate (EB) administration facilitated lordosis. EB had no clear effect on lordosis in strain 13 males. Progesterone after EB priming had no further facilitative effect in males of either strain. These results indicate that lordosis is more readily elicited from strain 2 than strain 13 males. Furthermore, lordosis in strain 2 males is not dependent upon gonadal hormones for its display although it is facilitated by EB (but not progesterone).

A prospective naturalistic study of electroconvulsive therapy in late-life depression.

We performed a prospective, naturalistic study using standardized clinical rating scales to characterize the effect of electroconvulsive therapy (ECT) on mood, cognition, and medical status in late-life depression. Over a 16-month period, 40 patients aged 60 years and over who fulfilled DSM-III criteria for a major depressive episode received a total of 42 ECT courses. Three patients (7%) developed significant medical complications: one had a syncopal episode due to arrhythmia, and two had symptomatic vertebral compression fractures. Confusion was noted during 13 courses (31%) and persisted at discharge in four (10%). More than half the patients were either psychotic or demented on admission, and all but three had been either unresponsive or intolerant to pharmacotherapy. All patients experienced a decrease in their depressive symptoms and more than two thirds were in complete or partial remission at discharge. Patients with psychotic depression experienced a greater improvement than patients with nonpsychotic depression, and patients with organic mental disorders experienced the same improvement as other patients. This study confirms that ECT is a safe and effective treatment of depression in late life.