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Electrochemical technologies have the potential to dramatically reshape the global energy landscape, but implementation at commercial scales has been slow. Technologies like fuel cells and electrolyzers are recently gaining more widespread traction and are being demonstrated at large scale. These developments are being fueled by the push to convert to energy carriers that can be produced without greenhouse gas emissions. However, technologies like electrochemical CO2 reduction, that involve more complicated chemistry and multi-step reaction mechanisms, are still far from industrial applications despite having been under development for decades. Progress in these more complicated systems is slow due to the multitude of variables that affect the reaction. Complex interactions between mass, charge, and heat transport, along with reaction kinetics are often convoluted and difficult to distinguish using traditional research methods. These methods rely on relatively small data sets and often use poorly characterized experimental systems that provide inconsistent results. For example, in electrochemical CO2 reduction research, mass transport effects have generally been overlooked in the study of different catalysts over the past decade. However, recent work has shown that what is measured in these electrochemical cells is not the intrinsic reaction kinetics, but rather the reactor kinetics that are dependent on the reactor geometry and its influence on the many factors involved in the reaction of interest. Designing experimental systems that can isolate specific phenomena will be extremely difficult, if not impossible. Thus, new methods must be developed to aid in the extraction of fundamental relationships governing the processes occurring in these experimental systems. This thesis explores how experimental electrochemistry can utilize methods inspired by Smart Manufacturing (SM) to accelerate the extraction of underlying relationships in complex electrochemical systems. In contrast to traditional experimental methods, SM techniques rely on large data sets to extract useful information from complex processes and optimize control. With large data sets of high quality data, modern computing capabilities can take advantage of computational methods in machine learning and multi-scale modeling to quickly draw hidden foundational relationships out of complex systems. Additionally, by utilizing sensing, data handling, and modeling techniques similar to those that will be used when an experimental technology is commercialized, this SM inspired approach can help to ensure that appropriate techniques are used when the technology is scaled up. First, the framework for the application of SM techniques to electrochemical research will be discussed, and brief demonstrations of its utility will be presented. The following chapters will provide more detailed discussion of computational fluid dynamics modeling efforts in the application of this framework to electrochemical CO2 reduction research and characterization of our experimental system. Finally, a second case where the framework has been applied to the development of an experimental system for testing electrochemical steam methane reforming will be discussed along with motivation for the development of this system. Together, these cases demonstrate how SM techniques can be applied in the lab to accelerate discoveries and provide an understanding of how they might be applied in other areas of research.

With increasing concern over the environmental impact of chemical manufacturing processes, a transition to synthesis methods that replace fossil fuel based processes with renewable electricity based processes is eminent. This work highlights the development of a high temperature proton conducting membrane reactor based on BZCY tubular membrane architecture which was designed and built to test the electrochemical SMR performance of BZCY membrane systems. Alongside this, an existing reactor system was retrofit to utilize Joule heating by applying an electric current directly through the FeCrAlloy reactor tube. CO2 methanation and SMR tests were performed, and results was compared between Joule heating and external heating by a furnace. Joule heating showed improved methane conversion and reaction rates up to twice that observed when externally heated by the furnace. Together, these systems provide new capabilities for testing electric based SMR that will aid future research in the Morales-Guio group.

Synthetic progestins such as medroxyprogesterone acetate (MPA) are used widely in the treatment of male sex offenders. In male cynomolgus monkeys (Macaca fascicularis) treated with testosterone (T), both MPA and progesterone (P) had comparable inhibitory effects on male sexual motivation and behavior. To determine if P, like MPA, decreases endogenous T levels, plasma T and P levels were analyzed in weekly blood samples (N=186) from eight intact males, each paired with a sexually receptive female before, during, and after treatment with subcutaneous Silastic P implants (336 behavior tests). P treatment decreased sexual activity but not plasma T levels. To ascertain if P, like MPA, acts by decreasing the nuclear uptake of T by brain, four P-treated and four control males were euthanized 60 min after intravenous injection of 3 mCi of [3H]T. The nuclear uptake of unchanged [3H]T and its metabolites [3H]E(2) and [3H]DHT was measured in samples of brain, pituitary gland, genital tract, and liver. P, unlike MPA, did not affect the nuclear uptake of [3H]androgens by brain, but reduced by 80% the nuclear accumulation of [3H]E(2) in tissue samples containing preoptic area and the anterior part of the bed nucleus of stria terminalis, although not in samples from hypothalamus or amygdala.

Bilateral lesions of the central tegmental field (CTF) in male rats virtually eliminate mating behavior. This study examined if mating-induced Fos expression (a measure of neuronal activation) and androgen receptors (AR) are colocalized in brain and spinal cord neurons which project to the CTF. Animals received unilateral injections of the retrograde tracer Fluorogold (FG) in the lateral part of the CTF (CTFl), and 10 days later were killed after ejaculating with females. Brains and spinal cords were examined for FG transport, AR-immunoreactivity (AR-ir), and Fos-immunoreactivity (Fos-ir). AR-ir and Fos-ir were visualized with fluorescence microscopy using cyanine-conjugated and fluorescein-conjugated secondary antibodies. The CTFl received projections from AR-containing neurons in forebrain structures (bed nucleus of stria terminalis, medial preoptic area, lateral and ventromedial hypothalamus), in the central amygdala and various mid- and hindbrain structures (dorsolateral tegmentum, superior and inferior colliculi, pedunculopontine nucleus), and in the lumbosacral spinal cord (lamina X). Some of the AR-containing neurons in bed nucleus of stria terminalis and in the dorsal part of the medial preoptic area with projections to the CTFl were activated by mating. Most AR-containing neurons in spinal lamina X with projections to the CTFl were also activated by mating. Information from spinal cord and pontine nuclei and from outputs descending from the forebrain may be relayed in the CTFl. Thus, as part of a network of hormone-sensitive neurons linking brain and spinal cord mechanisms for mating, the CTFl could participate in the integration of visceral and somatic information relevant for sexual behavior.

We describe the sex differences in the development of play initiation, rough‐and‐tumble play, and mounting behavior in rhesus monkeys. There are also sex differences in the acquisition and maintenance of dominance rank under naturalistic conditions in this female‐bonded, matrilineal society. The hormonal control of adult mating behavior, as well as the behavioral patterns expressed, are quite different in males and females, but both sexes have the capacity to show bisexual patterns of behavior in special circumstances. Using high‐performance liquid chromatography and autoradiography, we found a well‐marked system of neurons that can accumulate steroids in the hypothalamus and amygdala of the fetus by 120 days of gestation. In the male fetus, plasma testosterone is high at this time, so receptors are occupied. In contrast, plasma hormones in the female remain low throughout gestation. The natural masculinization of genetic male fetuses, as well as the masculinization of females whose mothers were administe...

In male cynomolgus monkeys the synthetic progestin, medroxyprogesterone acetate (MPA), decreases testosterone (T) levels and sexual behavior, binds to progestin receptors in brain, and reduces by about 70% the uptake of [3H]androgens by both brain and genital tract tissues. To examine the behavioral effects of progesterone (P) itself, eight castrated, T-treated males were each tested twice weekly with an estrogenized female before, during, and after they were treated with two SC Silastic P implants. Data from six 4-week treatment periods were analyzed to facilitate comparisons with our previous data using MPA: i) baseline, ii) weeks 4-7 of P treatment, iii) weeks 8-11 of P treatment, iv) weeks 1-4 after P implants were removed, v) weeks 5-8 after P withdrawal, and finally vi) weeks 9-12 after P withdrawal (384 1 h behavior tests). Weekly blood samples (N = 192) were analyzed by radioimmunoassay to determine plasma levels of both T and P. P treatment, which resulted in high plasma P levels (about 44 ng/ml), produced decrements in measures of male sexual behavior and motivation that were both qualitatively and quantitatively similar to those produced by MPA treatment but, unlike MPA, P did not decrease plasma T levels or change them in any way (about 850 ng/100 ml throughout). The findings suggest that P implants may be preferable to weekly MPA injections in the treatment of male sex offenders because they require less patient compliance and may not have MPA's troubling side effects.

The distribution of androgen receptor immunoreactive-neurons, mapped with the PG21 anti-androgen receptor antibody, was compared in male rat brains with the distribution of Fos-immunoreactive neurons induced by mating. In gonadally intact, but not in castrated male rats, substantial numbers of androgen receptor-containing neurons were present in a variety of forebrain and midbrain regions. The PG21 antibody apparently had a higher affinity for occupied than for non-occupied androgen receptors. Androgen receptor-immunoreactive regions included the medial preoptic area and other forebrain areas previously identified as containing androgen receptors, the dorsal and ventral periaqueductal gray, and a midbrain region that included the lateral part of the central tegmental field, part of the caudal zona incerta, the subparafascicular nucleus of the thalamus and the peripeduncular nucleus. Fos-expressive neurons were essentially absent in non-mated males but were present in the brains of rats which mated to ejaculation. All brain regions in which androgen receptor-immunoreactive neurons were counted also expressed Fos immunoreactivity after mating, and there was considerable overlap between the distributions of androgen receptor- and Fos-immunoreactive neurons. In a second experiment, we used immunofluorescent techniques to document the intraneuronal co-localization of Fos with androgen receptor immunoreactivity in the medial preoptic area, medial amygdala, and central tegmental field. In these regions mating-induced Fos immunofluorescence was exclusively localized in androgen receptor-immunofluorescent neurons. However, not all androgen receptor neurons were Fos expressive, suggesting that only some androgen-sensitive neurons were activated during mating. These results are consonant with the view that hormone actions on forebrain and midbrain structures influence the neuronal activity correlated with mating.

We previously reviewed the effects of gonadal hormones on the sexual and aggressive behavior of macaques as observed in field, outdoor colony, and laboratory studies. There were consistent similarities between findings from different observational settings, but there were also noteworthy differences which suggested the importance of social and environmental factors in modulating the effects of hormones. We now examine the role of these factors further and consider the extent to which partner preferences, familiarity between individuals, and also dominance rank can affect the behavior of male-female pairs and thereby modify the influences of hormones. The evidence suggests that all these factors are important. Hormone-dependent short-term partner preferences appear to be critical for the formation of consort bonds and to facilitate mating between unfamiliar partners. Socially based partner preferences tend to dampen hormonal influences and may lead to long-term familiarity. Long-term familiarity decreases sexual interactions and may be a proximate mechanism underlying incest avoidance and periodic male troop transfers. Both males and females exhibit mate competition under certain conditions, and their dominance rank can modify sexual and aggressive behavior by either optimizing or reducing hormone-dependent changes. These interaction effects between social and hormonal variables also have relevance for the design and interpretation of laboratory experiments. © 1996 Wiley-Liss, Inc.

Copulatory behavior was studied in five groups of sexually experienced, gonadally intact male rats in which: (i) the nonsteroidal aromatase inhibitor Fadrozole (CIBA-Geigy CGS 16949A) was delivered bilaterally (0.756 microgram in 6.0 microliters saline in 24 h to each side) into the medial preoptic area (POM) together with normal saline given s.c. via osmostic minipumps (n = 10); (ii) normal saline was delivered bilaterally into POM together with the same dose of Fadrozole s.c. (n = 9); (iii) Fadrozole was delivered bilaterally into the lateral preoptic area together with normal saline given s.c. (n = 6); (iv) Fadrozole was delivered bilaterally into the cerebral cortex together with normal saline given s.c. (n = 6), and (v) unoperated controls (n = 14). Mounting and ejaculation were significantly decreased in rats receiving Fadrozole in POM compared with the behavior of rats in the other 4 groups. Few differences occurred between rats in the latter 4 groups, all of which continued to mate. The H222 and ER-715 anti-estrogen receptor (ER) antibodies were used to examine the distribution of ER immunoreactive (ERir) neurons in hypothalamic and limbic sites in gonadectomized controls and in some of the rats in groups i, ii and v. Since labeling of ERir neurons in rat brain with the H222 anti-ER antibody is reported to be inhibited by estrogen, it was used here to identify regions (with staining) where the aromatization of testosterone (T) into estradiol (E2) had been suppressed. Intense H222 ERir nuclear neuronal labeling was confined to the POM of males receiving Fadrozole in POM, and significantly more labeled neurons were found in the POM of these rats than in the POM of rats treated with saline in POM. In contrast, the ER-715 antibody, which is reported to stain neurons independently of hormonal status, labeled neuronal nuclei in hypothalamic and limbic regions of all groups, demonstrating the presence of ER. These findings show that conversion of T into E2 in the POM of the male rat is important for male rat copulatory behavior and that H222 ERir nuclear neuronal labeling can be used to identify the neurons in POM that were affected by Fadrozole.

The H222 and ER-715 anti-estrogen receptor (ER) antibodies were used to examine the distribution of ER immunoreactive (ERir) neurons in hypothalamic and limbic sites of: (i) castrated male rats; (ii) castrated males implanted s.c. with silastic capsules containing testosterone (T), and (iii) castrated males receiving T together with 0.25 mg/kg/day of the nonsteroidal aromatase inhibitor, fadrozole (CIBA-Geigy CGS 16949A), delivered s.c. by means of implanted osmotic minipumps. Because labeling of ERir neurons in rat brain with H222 anti-ER antibody is reported to decrease when estrogen is present, it was used here to determine whether or not estrogen derived from the aromatization of T would affect ERir neuronal labeling. Castrated males showed H222 ERir-positive neurons in the lateral septum, medial preoptic area, several subdivisions of the hypothalamus, amygdala, and bed nucleus of stria terminalis. In contrast, in T-treated castrates, H222 ERir labeling was either eliminated or greatly reduced in all brain areas with the exception of the lateral septum. In castrated male rats given T together with fadrozole, H222 ERir labeling was restored in all brain areas where it had been reduced by T treatment. The ER-715 antibody effectively labeled neurons in all brain regions independently of the treatment condition, indicating that ER was present in the brains of animals in all treatment groups. These findings point to functional differences in ER dynamics in brain areas implicated in the control of sexual behavior by male rats.(ABSTRACT TRUNCATED AT 250 WORDS)

In many vertebrates, castration and hormone replacement and, more recently, the use of aromatase inhibitors, have shown that male sexual activity is mediated by the aromatization of testosterone (T) to estradiol (E2). In macaques, however, the systemic administration of E2, either alone or in combination with androgen, failed either to maintain or to restore the sexual activity of castrated males. The present study examines the effects of administering the nonsteroidal aromatase inhibitor, Fadrozole, either alone or combined with E2, to castrated, T-treated male cynomolgus monkeys at a dose of 0.25 mg/kg/day. This dose inhibited by over 98% the conversion of T to E2 and the subsequent accumulation of the latter in hypothalamic cell nuclei. Castrated males bearing sc Silastic impants of T were each tested with an ovariectomized, E2-treated female partner before, during, and after being given minipumps delivering either Fadrozole or water (240 1-hr tests). Within 2 weeks, Fadrozole significantly reduced ejaculatory activity and male sexual motivation in the absence of changes in plasma T levels, which remained in the upper range for intact males. Additional estradiol treatment produced small but significant increases in ejaculations by three of the six males only, and measures of male sexual motivation remained unchanged (120 tests). The present results, which stand in contrast to our previous findings in macaques, support the view that aromatization of T is important for ejaculatory activity and sexual motivation in a male primate. They also suggest that exogenous E2, which reaches the brain from the systemic circulation, does not fully duplicate the behavioral effects of E2 produced locally in the brain by the aromatization of T.

One group of male rats was trained to associate novel odors with three different environmental conditions: the presence of (i) a sexually receptive female (RF), (ii) an unreceptive female (UF) and (iii) no other rat (NO). A second group of males received no training. Single units in nucleus accumbens (NAC) were then recorded in anesthetized animals and their responsiveness to various odors was tested. Odors that had been associated with receptive females during training evoked significantly more unit responses in NAC than did the same odors in untrained males. There were no differences between trained and untrained males in the numbers of units responsive to odors associated with unreceptive females and with the empty training chamber. In trained animals, both the percentage of responding units and the magnitude of olfactory-evoked responses were significantly larger with RF-associated odors than with either UF or NO odors. Both of these effects were more pronounced in rats that had ejaculated with females during training than in rats that had not. Findings demonstrated that pairing odors with the presentation of sexually receptive females enhanced the responsiveness of NAC neurons to those odors and indicated a role for NAC in associating environmental stimuli with natural reward processes.

Rats were implanted with stimulating electrodes aimed at the medial forebrain bundlelateral hypothalamus (MFB-LH) and were trained to lever-press for brain stimulation on a fixed-interval 15-sec schedule of reinforcement. When behavior had stabilized, the animals were tested with graded doses of d-amphetamine (0.1–1.0 mg/kg), cocaine (3.0–30 mg/kg), and nomifensine (1.0–10 mg/kg). Separate groups of animals were tested in a locomotor activity procedure over the same dose ranges. All three drugs produced graded increases in rates of responding which ranged from 180–295% of saline control levels following the highest dose of each drug. In contrast, there were no significant changes in numbers of reinforcements at any of the doses used. When tested in a locomotor activity device, all three drugs produced similar increases in activity with increasing dosage. Although currently little used, the fixed-interval schedule of brain self-stimulation can be helpful in making comparisons of the stimulant properties of abused drugs, such as amphetamine and cocaine, and less well-known drugs with abuse potential such as nomifensine. © 1992 Wiley-Liss, Inc.

In nonhuman primates, surgical castration reduces plasma testosterone levels and male sexual behavior, and testosterone replacement restores them. Chemical castration with compounds that lower plasma testosterone levels is used clinically in the treatment of certain forms of cancer and to reduce aberrant sexual behavior in male sex offenders. In the United States, medroxyprogesterone acetate (MPA) is the drug most used to help reduce serious sexual behavioral problems in men. We were therefore interested in comparing the behavioral effects of MPA treatment (40 mg once a week) in 4 intact male cynomolgus monkeys (4 pairs, 120 tests) with data from an earlier study in our laboratory on 4 males observed before and after surgical castration (16 pairs, 192 tests). Both MPA treatment and surgical castration reduced plasma testosterone to very low levels and decreased ejaculatory activity, but MPA treatment additionally affected measures of male sexual motivation (decreased numbers of male mounting attempts and increased mounting attempt latencies) which were not primarily affected by surgical astration. However, surgical castration decreased intromission ability (percentage of intromitted thrusts per test) and male yawning behavior more rapidly than did MPA treatment. This suggested a hypothesis that different mechanisms could be involved in the behavioral effects-namely, that surgical castration may act primarily via testosterone-dependent peripheral mechanisms, while chemical castration with MPA does so primarily via central mechanisms regulating sexual motivation.

Rats were implanted with stimulating electrodes in the medial forebrain bundle-lateral hypothalamus (MFB-LH). After recovery from surgery, they were assigned to one of two groups equalized for body weight. One group was housed four animals to a cage and animals in the other group were housed individually. After four weeks in these housing conditions, animals were tested during the fifth week for locomotor activity in five daily 15-min sessions, and their reactivity to handling was also measured. During the sixth and seventh weeks, animals were allowed to self-train for brain stimulation (ICSS) during daily 15-min sessions. Animals housed in groups had higher levels of locomotor activity and were less reactive to handling than were animals housed individually. When tested for the acquisition of ICSS, animals housed as a group made more responses than did animals housed individually. These results indicate that, within the time frame of a few weeks, the housing conditions of adult animals caused differences in both unconditioned behavior, such as locomotor activity, and in the acquisition of a highly reinforcing brain self-stimulation task.

Microinjections of substance P (SP) into the ventral tegmental area (VTA) increase locomotor activity in rats, and this effect is thought to be produced by activation of the mesolimbic dopamine system. In the present study, firing rates of neurons in areas receiving projections from the mesolimbic dopamine system were recorded during injections of SP (3 microgram in 0.5 microliters saline) into the VTA of rats anesthetized with chloral hydrate. Significant changes in firing rates were observed in 84% of the units recorded in nucleus accumbens and olfactory tubercle. There were mostly decreases in nucleus accumbens (NAC, 21 of 25 units affected by SP) and mostly increases in olfactory tubercle (OT, 13 of 18 units affected by SP). In contrast, neither saline injections into VTA nor SP injections 2 mm dorsal to VTA had any effect on NAC or OT neurons. Haloperidol (0.5 mg/kg IV) blocked the effects of SP, suggesting that effects were mediated, at least in part, by the mesolimbic dopamine system. Results indicated that activation of dopaminergic neurons by SP injections into VTA can produce changes in the activity of neurons in NAC and OT, areas which receive mesolimbic dopaminergic projections.

The synthetic progestin, medroxyprogesterone acetate (MPA), is used to treat male sex offenders, and it is also suppresses sexual activity in male monkeys. To examine the possibility that MPA may act as an anti-androgen in the primate brain, 4 intact male cynomolgus monkeys were given MPA (40 mg i.m.) once a week for 16 weeks, while 4 control males received i.m. injections of vehicle. All males were then castrated and 3 days later were given 3 mCi [3H]testosterone ([3H]T) i.v.; 1 h after injection males were killed, and radioactivity in nuclear pellets obtained from the hypothalamus (HYP), preoptic area (POA), amygdala (AMG), septum, pituitary gland and genital tract was analyzed by HPLC. Concentrations of [3H]T and [3H]dihydrotestosterone in nuclear pellets were 65-96% lower in MPA-treated males than in controls (P less than 0.001), but the aromatized metabolite, [3H]estradiol, which was the major form of radioactivity present in nuclear pellets from HYP, POA and AMG, was unchanged. There were no differences in concentrations of [3H]T in supernatants from the tissues of MPA-treated and control males. Because the reduced nuclear uptake of androgen in brain occurred in males whose androgen-dependent behavior had been suppressed by MPA treatments, it is proposed that MPA may have anti-androgenic effects at the level of the cell nucleus in brain regions that control behavior.

It is well known that neurons of the nigrostriatal dopamine (DA) system respond to sensory stimuli, and our primary objective here was to ascertain if neurons in the terminal regions of the mesolimbic DA system respond to sensory input also. In addition, the effects of electrical stimulation of the ventral tegmentum, which contains the DA cells of origin of the mesolimbic system, on sensory-evoked responses in mesolimbic neurons was studied. In rats anesthetized with chloral hydrate, responses of single units to olfactory and somatosensory stimuli were recorded in 6 forebrain regions including nucleus accumbens and olfactory tubercle. Both increases and decreases in spontaneous firing rates were evoked in 225 of 336 units by one or more of the 8 types of sensory stimuli employed (5 olfactory, 3 somatosensory). Excitatory responses occurred twice as frequently as inhibitory responses, but a few units responded with excitatory responses to some stimuli and inhibitory responses to others. The proportions of units responsive to olfactory and/or somatosensory stimuli were different in different regions. After electrical stimulation of the ventral tegmentum, sensory-evoked responses were changed in 30 of the 49 units tested (61%). There were increases, decreases or combinations of a decrease followed by an increase in sensory-evoked responses, which persisted for 1–10 min after the application of a single electrical stimulus train. Haloperidol (0.3 mg/kg, i.p.) either blocked the effect of tegmental stimulation or decreased all responses. The present results demonstrated that units in the terminal regions of the mesolimbic DA system are responsive to sensory input and that these responses can be affected by prior electrical stimulation of the ventral tegmentum.

Rats were implanted with stimulating electrodes aimed at the medial forebrain bundle-lateral hypothalamus (MFB-LH) and were trained to lever-press for brain self-stimulation on a fixed interval: 60 s schedule of reinforcement. The effects of graded doses of naloxone (0.1-30 mg/kg), morphine (0.3-5.6 mg/kg), naloxone plus morphine, d-amphetamine (0.03-1.0 mg/kg), naloxone plus d-amphetamine, phencyclidine (0.3-5.6 mg/kg), and naloxone plus phencyclidine were tested. Naloxone produced a significant decrease in rates at 30 mg/kg. Naloxone (0.1-1.0 mg/kg) plus morphine blocked the dose-dependent decrease produced by morphine alone. In contrast, naloxone (1.0-10 mg/kg) plus d-amphetamine attenuated the graded increase in response rates produced by d-amphetamine. Naloxone (1.0-10 mg/kg) plus phencyclidine did not reliably change the increase in response rates produced by phencyclidine alone. The use of the fixed interval schedule of brain self-stimulation to study these drug interactions is novel, and further demonstrates that the highly reinforcing aspects of brain stimulation, known to be influenced by dopamine, may also be modulated by the endogenous opiate system.

The effects of amphetamine on the extinction of intracranial self-stimulation (ICSS) and on postextinction ICSS performance were examined in rats implanted with electrodes either in medial prefrontal cortex (mPFC) or in the posterior hypothalamus-ventral tegmental area (PH-VTA). Lever-pressing for ICSS was allowed to stabilize in daily 15-minute sessions before each animal was exposed to 5 minutes of extinction (responding without reward). Animals were administered either 0.25 mg/kg d-amphetamine or saline before baseline, extinction and lower in PH-VTA animals compared with saline-treated controls. Rates did not change immediately after extinction but, one day later, postextinction sessions. After amphetamine treatment, the number of lever presses during extinction was higher in mPFC animals and rates had increased in all saline-treated animals (both PH-VTA and mPFC animals) and had decreased in all amphetamine-treated animals. These findings demonstrated that the effects of amphetamine on the extinction of ICSS were different in cortical and hypothalamic sites, possibly because of regional differences in stimulus-evoked reinforcement and inhibitory processes.

Eight groups of rhesus monkeys each consisting of one male and four ovariectomized females were observed while two of the females were treated with hormones to produce artificial menstrual cycles. These were either synchronized or offset by 7-day increments. Sexually preferred females, defined by the numbers of ejaculations per test, received almost twice as many ejaculations as did non-preferred females during all synchronized and offset cycles and during all cycle phases. However, short-term changes in partner preference occurred when the midcycle phase of non-preferred females coincided with the middle or late progesterone phase of preferred females, suggesting a negative effect of progesterone on behavior during the menstrual cycle. There were highly significant differences between preferred and non-preferred partners for almost all of their sexual and social interactions, and preferred partners showed longer proximity and grooming times as well as higher levels of sexual activity. Partner preferences accounted for more of the behavioral variance between pairs than did female dominance, although males sought the proximity of dominant females independently of their partner preferences. Thus, in a setting uncomplicated by male mate competition, sexual preference by male rhesus monkeys is a robust phenomenon depending on complex interactions between dominance, hormonal status, and the individual behavior of female partners.

To examine whether estradiol might be effective in maintaining sexual behavior after castration or after testosterone withdrawal, we have observed male rhesus monkeys during daily 1-hr tests alternately with each of two ovariectomized, estradiol-treated females (four males, four females, eight male-female pairs, 798 tests). Estradiol (2-5 micrograms/kg sc/day) or vehicle was administered in counterbalanced order immediately after castration and again immediately after withdrawal of testosterone propionate treatments (800 micrograms and 1.6 mg sc/day). There were no significant differences in behavior during vehicle and estradiol treatments to indicate that estradiol helped to maintain male sexual activity. Instead, estradiol treatment tended to interfere with the capacity to intromit. This supported the results of other studies, namely, that the systemic administration of estradiol does not enhance the sexual behavior of castrated male macaques, and raises questions about the role of both aromatization and estrogen receptors in the male primate brain.

Testosterone secreted by the testis of the macaque fetus is thought to influence certain aspects of the brain’s subsequent development which may be responsible for the ontogeny of sexually dimorphic p

Medroxyprogesterone acetate (MPA), a synthetic progestin that reduces plasma testosterone levels, has been used in the treatment of male sex offenders. It also reduces the sexual activity of male macaques. To investigate its sites and mechanisms of action, 11 adult male cynomolgus monkeys were castrated and 7 and 21 h later were pretreated with 20 mg progesterone s.c. (Prog, n = 3), or 5 mg dihydrotestosterone propionate s.c. (DHTP, n = 3) or oil vehicle (controls, n = 5). Twenty-four hours after castration, all males were injected i.v. with 5 mCi [3H]-MPA, and killed after 60 min. Left halves of the brains were processed for thaw-mount autoradiography to identify the neurons accumulating radioactivity, and right halves were analyzed by high performance liquid chromatography (HPLC) to measure the uptake of [3H]-MPA in nuclear fractions. In males pretreated with oil, there were labeled neurons in the ventromedial nucleus (n.), arcuate n., medial preoptic n. and anterior hypothalamic area. In progesterone-pretreated males, labeling was reduced by 84-100% compared with controls (p less than 0.001), but in DHTP-pretreated males there was no effect, and labeling was not significantly different from control levels. Nuclear concentrations of [3H]-MPA measured by HPLC in controls were highest in the hypothalamus, amygdala, preoptic area and pituitary gland. Pretreatments with progesterone reduced the nuclear concentrations of [3H]-MPA in hypothalamus, preoptic area and pituitary gland by 82-95% compared with controls (p less than 0.05), but DHTP pretreatments had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

In contrast to some other species, the numbers of activated neurons in the brains of male and female macaques are high in both mated and unmated animals. Dual labeling with the 1D5 anti-estrogen receptor antibody and the c- fos polyclonal anti-c- fos antibody was used in 19 female cynomolgus monkeys to examine whether mating selectively increases the activation of neurons containing estrogen receptors (ER). Mated females, and social controls exposed to males without mating, were euthanized about 75 min after the start of the test, exactly 60 min after the first ejaculation (mated females, N = 7) and 75 min after the start of exposure to a male (social controls, N = 4). A second control group of unmated females ( N = 8) remained in their individual cages until euthanasia. Neuronal nuclei containing Fos immunoreactivity (Fos-ir) alone, ER-immunoreactivity (ER-ir) alone, or both Fos-ir and ER-ir, were counted in 8 brain regions, but 2 of these regions contained too few ER-ir neurons to permit analysis. The proportion of ER-ir neurons colocalizing Fos-ir was significantly higher in the preoptic area ( P = 0.027) and ventromedial hypothalamus ( P = 0.04) of mated than of control females, suggesting the selective activation of ER-containing neurons by mating in these two brain regions known to be important in the control of female mating. The proportion of Fos-ir neurons not containing ER-ir was significantly lower in the cortical amygdala ( P = 0.045) of mated than in control females, suggesting a selective deactivation of neurons not containing ER-ir.

Mating activates estrogen sensitive neurons in several regions of male rat brain, including the medial amygdala (MEA). Infusion of the aromatase inhibitor, Fadrozole, into the MEA reduced mating, presumably by inhibiting conversion of testosterone (T) to estradiol (E(2)). We investigated whether administering E(2) locally into the amygdala (AMG) would maintain sexual behavior in male rats given systemic Fadrozole to eliminate E(2) elsewhere in the brain. Gonadally intact male rats were divided into two matched groups, based on ejaculatory performance in weekly tests with receptive females. All males received 0.29 mg/kg/day sc Fadrozole and bilateral implants to AMG. E(2)-in-AMG males (N=6 experimentals) received implants tipped with a cured mixture of E(2) in Silastic Medical Adhesive, whereas Vehicle-in-AMG males (N=6 controls) received implants tipped with cured adhesive alone (without E(2)). In E(2)-in-AMG males, postoperative mount and intromission frequency did not differ significantly from pretreatment baseline levels, but ejaculation frequency declined significantly (P.01). Conversely, in Vehicle-in-AMG males, postoperative mounts and intromissions (P.01) and ejaculations (P.01) declined significantly. Postoperative mount and intromission frequency of Vehicle-in-AMG males was significantly lower than that of E(2)-in-AMG males (P.01), but ejaculation frequency did not differ significantly between groups. This suggests that E(2)-sensitive AMG neurons are important for sexual arousal but not ejaculatory performance.

The theoretical foundation of ethology is that behavior, like morphology, is adaptive and subject to selection pressures, and that it may have a genetic basis and phylogenetic history. As with morphological and anatomical features, a behavioral trait can best be understood by determining (1) the physiological and environmental factors regulating it (its immediate or proximate mechanisms), (2) its development in the individual (ontogeny), (3) its function in terms of the advantages it confers on the animal, and (4) its evolutionary development (phylogeny).

A critical task for all living organisms is to obtain from their environment the nutrients required for energy expenditures, growth, and reproduction, and, in the short term, to maintain by homeostatic processes the constancy of the internal milieu. These various needs are mediated by behavioral mechanisms such as appetite and hunger, which lead to food-seeking behavior. Particularly in the human, these mechanisms can go awry and this results in disturbances in the control of body weight, leading to obesity or starvation.

Reproduction encompasses behaviors that range from the identification and courtship of a suitable mate to the successful rearing of offspring. Behavioral mechanisms determine the social, mating, and parental care systems of a particular species, and depend on complex interactions between anatomy and physiology on the one hand, and environmental factors, notably, habitat and predation, on the other. For example, high predator pressure may promote greater defense of young and, in turn, the extent to which the male can effectively contribute to this defense helps to determine the mating system (Chapter 15).

Chapter 2 dealt with specializations in the sender of signals, but there are also genetically programmed specializations in the receiver of signals coming from the environment or from social companions. So there can be a genetic basis for receiving as well as sending signals with adaptive significance. This is important because of the many hundreds of bits of sensory information with which animals are bombarded every moment of the day and night. Specialization in the receiver requires information reduction brought about by selective filtering, which helps to separate relevant from irrelevant information. This filtering can be considered on two separate levels: perception and attention.

Animals need to orient themselves to various environmental stimuli to find shelter (nests, lairs, burrows), food, and mates, to nurture their young, to escape predators, and, the primary topic of this chapter, to stay within or return to favorable environments. Orientation as used here comprises turning the body in a particular direction, together with movement over short distances, while navigation is the term reserved for long-distance travel, including migration. Orienting stimuli can involve several different sensory modalities. Visual stimuli include the sight of mates, predators, or prey in many birds. Acoustic stimuli are used in echolocation by bats and porpoises to avoid obstacles and find prey. Chemical stimuli include insect and mammalian pheromones that are used to locate mates. Tactile signals enable male clawed frogs to detect an appropriate mate. Sharks use electrical fields to detect prey buried in sand, while certain snakes use thermal cues to detect warm-blooded prey. In addition to signals produced by animals, a variety of other exteroceptive cues, such as gravity, light, temperature, barometric pressure, humidity, magnetic fields, and air and water currents, can serve as orienting stimuli within an animal’s immediate environment.

The attempt to understand and classify the behavior of animals, and in particular that of humans, has engaged scholars for many centuries, at least since the time of the Greek philosophers Aristotle and Plato. Ethology developed from zoology, that is, from the study by naturalists of animals in their natural habitat, whereas psychology developed from philosophy. Much of the difference between the theoretical and methodological approaches taken by ethologists and psychologists can be traced to their different origins. The following sections briefly summarize the principal branches of the behavioral sciences, ethology, and comparative psychology, the controversies between them during the 1950s and 1960s, and the subsequent synthesis that has developed into the modern study of animal behavior. This may be the most difficult chapter in the book to master.

Trivers (1972) defined parental investment as “any investment by the parent in an individual offspring that increases that offspring’s chances of surviving (and hence reproductive success) at the cost of the parent’s ability to invest in other offspring.” This includes investment in the survival of gametes and embryos as well as in the parental care of offspring after hatching or birth, until they become independent. In many species, parental care is virtually absent: In some fish, huge numbers of eggs and sperm are released into the water during spawning; fertilization and the survival of eggs and hatchlings are left to chance. In other species, the female, the male, or both provide parental care by (1) ensuring a food supply; (2) regulating the immediate environment, for example, fish fanning eggs to provide oxygenated water and birds incubating eggs; and (3) protecting the offspring from predators; and, in animals with complex brains, by (4) serving as models for acquiring social and hunting skills. Provision of food can involve quite bizarre mechanisms, including the cannibalization of eggs and younger embryos within the mother’s oviduct by other sand shark embryos, so that usually only one embryo remains. Female digger wasps lay an egg into a paralyzed, but not dead, honeybee upon which the larva feeds. In an African species of social spider, the mother makes the supreme sacrifice by being totally devoured by her young. Protection from predators can also take an unusual form. In an African mouth-breeding cichlid fish, Haplochromis, the female picks up her eggs with her mouth immediately after laying them and simultaneously picks up male sperm during attempts to pick up the “dummy” eggs on the anal fin of the male. Fertilization, incubation, and hatching all occur within her mouth, to which the fry continue to return at night and when threatened.

The following discussion assumes that the reader has taken a course in introductory and Mendelian genetics and has a basic understanding of its terminology, principles, and role in evolution. Briefly, within the nucleus of every cell except the gametes, most species have pairs of homologous chromosomes, each consisting of a long strand of the molecule deoxyribonucleic acid (DNA), with a centromere near one end. One chromosome of each pair is derived from the father and the other from the mother, and both contain the same gene sequence. Perhaps the most important discovery in biological science during the twentieth century, for which the 1962 Nobel Prize for Physiology or Medicine was awarded to Watson, Crick, and Wilkins, was the structure of DNA, a double helix consisting of two intertwined sugar-phosphate strands connected by a series of four bases, adenine pairing with thymine, and cytosine with guanine (Watson & Crick, 1953). This structure showed how chromosomes replicate themselves, and thereby the genetic code they contain, during cell division. Chromosomes consist of many genes, each being a section of chromosome at a specific locus that contains instructions for producing a particular protein that, together with others, helps to determine the development, structures, and physiological functions of the organism. In addition to the autosomes, there are two sex chromosomes that are heterologous in one sex, for example, XY in male mammals and WZ in female birds. Humans have 46 chromosomes, 22 pairs of homologous autosomes, together with a pair of sex chromosomes.

Mating was studied in sexually experienced, gonadally intact male rats assigned to two surgical groups matched on the basis of mean mounting frequency during behavioral screening trials conducted prior to the study. Estradiol (E 2 ) was delivered bilaterally into the medial preoptic area (MPO) of experimental males by means of hormone-coated implants, and fadrozole was given sc (0.25 mg/kg/day) via osmotic minipumps to block E 2 formation from testicular testosterone throughout the brain. Control males received blank bilateral implants in the MPO and sc fadrozole. After the completion of behavioral testing, immunocytochemical comparisons of the brains from experimental and control rats were made using the H222 antiestrogen receptor (ER) antibody, whose labeling is inhibited by the presence of E 2 . The histology demonstrated that E 2 was confined exclusively to the MPO of experimental males but was absent throughout the brains of controls. In controls, mounting decreased significantly by the 7th day after surgery compared with presurgical levels and did not recover. In contrast, on all postsurgical days, the mounting frequency of the experimental group was significantly higher than that of controls. Although experimental males also showed an initial, significant postsurgical decline in mounting frequency, it recovered completely by the 28th postoperative day. Ejaculations declined significantly after surgery in both groups but, unlike in controls whose performance remained low, ejaculations in experimental males partially recovered and were significantly higher than in controls during the postoperative period. Results showed that ER-containing neurons in the MPO influence male rat copulatory behavior.

The c-fos polyclonal anti-c-fos antibody was used to examine the effects of mating on Fos expression in brain neurons of 11 male macaques. Behavior tests were for 30 min, five males were unmated, four were mated, and two were social controls. Mated males were killed 60 min after ejaculation. Social controls were paired with females, but mating did not occur. Fos immunoreactive (Fos-ir) neuronal nuclei were counted in nine brain regions extending from the medial preoptic to the mammillary body area of all males. In contrast to previous reports on nonprimate laboratory species, overall there was as much Fos-ir in unmated as in mated males. Moreover, there was significantly less Fos expression in four brain regions (known to contain steroid receptors), namely, ventromedial hypothalamus, arcuate nucleus, lateral mammillary area, and bed nucleus of stria terminalis, of mated than of unmated males. There were no significant differences between mated and unmated males in the 5 other brain regions studied. These findings may reflect taxonomic differences between primates and nonprimates, or result from greater neural activation in feral animals maintained in a laboratory than in domesticated, inbred laboratory species. The simplest interpretation would be that neural activity in the male primate is turned off by mating in some brain sites but not in others.

This study was designed to determine the extent to which Fos immunoreactivity (induced either by mating or noncontact sociosexual interaction) and androgen receptor (AR) immunoreactivity are colocalized in brain and spinal cord of male rats. Some males (Mated) were allowed to mate to ejaculation; others (Social Controls) were placed with females but physical contact was prevented by a wire mesh screen; remaining males (Isolated) were placed alone in the test jar for the duration of the test period. After testing, brains and spinal cords were examined for AR and Fos immunoreactivity (ir). PG21 anti-AR and anti-c-fos primary antibodies were visualized by fluorescence microscopy using cyanine-conjugated and fluorescein-conjugated secondary antibodies. In both brain and spinal cord, the number of Fos-ir neurons varied according to group: Mated males > Social Controls > Isolated males. Fos was highly localized in subsets of AR-ir neurons within the medial preoptic nucleus, bed nucleus of the stria terminalis, dorsomedial nucleus of the amygdala, and central tegmental field. Fos was also localized in subsets of AR-ir neurons within the L5, L6, and S1 segments of the spinal cord. Spinal cord concentrations of AR-ir and Fos-ir neurons were greatest in Lamina X, and the vast majority of Fos-ir neurons in the dorsal part of Lamina X were also AR-ir. Thus, in both brain and spinal cord, androgen-sensitive neurons are active during mating, and transmission of sexually relevant information from cord to brain is probably accomplished via hormone-sensitive spinal neurons.

Conversion of testosterone into estradiol is important for male rat sexual behavior, and both steroids probably contribute to mating. The distributions of neurons containing androgen receptors (AR) and estrogen receptors (ER) overlap, and many AR-immunoreactive (AR-ir) neurons express Fos immunoreactivity (Fos-ir) induced by mating. Because mating-induced Fos-ir in the male rat occurs mainly in AR-ir neurons, and because both steroids are important for mating, we hypothesized that (i) AR-ir and ER-ir are colocalized and that (ii) some of these neurons are activated during mating. We examined, in adjacent sections from the medial preoptic area (MPN) through the central tegmental field (CTF), the expression of ER-ir in: (i) AR-ir-containing neurons, and (ii) Fos-ir-expressive neurons. PG21 anti-AR, OA-11-824 anti-c-fos, H222 or 1D5 anti-ER primary antibodies were visualized, respectively, with cyanine-conjugated, fluorescein- or cyanine-conjugated, and fluorescein-conjugated secondary antibodies in male rats which were killed 1 h after ejaculating with a receptive female. In MPN, bed nucleus of the stria terminalis (BNST), and medial amygdala (MEA), 80–90% of ER-ir labeling occurred in AR-ir-positive neurons but only about 30% of AR-ir neurons were ER-ir-positive. No ER-ir was found in the CTF. This suggests the presence of three types of brain neurons sensitive to gonadal steroid hormones: neurons sensitive to androgens only, neurons sensitive to both androgens and estrogens, and neurons sensitive to estrogens only. About 50% of ER-ir labeling occurred in cells expressing mating-induced Fos-ir but only about 30% of Fos-ir neurons were ER-ir-positive. These findings suggest that, in the MPN, at least two different neuronal populations are activated during mating: the first contains AR-ir only and the second contains AR-ir and ER-ir. In the BNST and MEA, at least three hormonally sensitive populations are activated during mating: the two described above plus a third population which expresses ER-ir only.

Sexual motivation and behavior decreased in male cynomolgus monkeys given either Depo-Provera (medroxyprogesterone acetate, MPA), which reduces androgen uptake by brain, or the nonsteroidal aromatase inhibitor, Fadrozole, which virtually eliminates the conversion of testosterone (T) to estradiol (E2) in brain. This suggested that both unchanged T and E2 are important for the control of male primate sexual behavior, but combined treatment with MPA and Fadrozole did not have the anticipated summatory effects in intact males: the behavioral decrements when MPA-treated males were given Fadrozole were about half those observed when Fadrozole was given alone. The present study tested the hypothesis that Fadrozole suppressed the behavioral effects of MPA by preventing the induction by E2 of progestin receptors in the brain to which MPA binds. Eight castrated, T-treated males were each tested with an estrogenized female i) during baseline, ii) during MPA treatment, iii) during treatment with MPA and Fadrozole together, and iv) with E2 treatment added to condition (iii) (256 1-h behavior tests). All dosages were those used in previous studies. Sexual motivation, as reflected in mounting attempts and mounting attempt latencies, was further diminished by E2 treatment in males receiving both MPA and Fadrozole, but ejaculatory activity was not changed. Immunocytochemistry demonstrated that the distributions of progestin and androgen receptors were little affected by MPA treatment, and that progestin receptor immunoreactivity was almost completely abolished in the brains of males receiving both MPA and Fadrozole but present in those receiving additional E2 treatment, findings that supported the hypothesis.