Leonardo da Vinci's "A skull sectioned": skull and dental formula revisited.

What can be learned from historical anatomical drawings and how to incorporate these drawings into anatomical teaching? The drawing "A skull sectioned" (RL 19058v) by Leonardo da Vinci (1452-1519), hides more detailed information than reported earlier. A well-chosen section cut explores sectioned paranasal sinuses and ductus nasolacrimalis. A dissected lateral wall of the maxilla is also present. Furthermore, at the level of the foramen mentale, the drawing displays compact and spongious bony components, together with a cross-section through the foramen mentale and its connection with the canalis mandibulae. Leonardo was the first to describe a correct dental formula (6424) and made efforts to place this formula above the related dental elements. However, taking into account, the morphological features of the individual elements of the maxilla, it can be suggested that Leonardo sketched a "peculiar dental element" on the position of the right maxillary premolar in the dental sketch. The fact that the author did not make any comment on that special element is remarkable. Leonardo could have had sufficient knowledge of the precise morphology of maxillary and mandibular premolars, since the author depicted these elements in the dissected skull. The fact that the author also had access to premolars in situ corroborates our suggestion that "something went wrong" in this part of the drawing. The present study shows that historical anatomical drawings are very useful for interactive learning of detailed anatomy for students in medicine and dentistry.

The regulation of brain states by neuroactive substances distributed via the cerebrospinal fluid; a review.

The cerebrospinal fluid (CSF) system provides nutrients to and removes waste products from the brain. Recent findings suggest, however, that in addition, the CSF contains message molecules in the form of actively released neuroactive substances. The concentrations of these vary between locations, suggesting they are important for the changes in brain activity that underlie different brain states, and induce different sensory input and behavioral output relationships.The cranial CSF displays a rapid caudally-directed ventricular flow followed by a slower rostrally-directed subarachnoid flow (mainly towards the cribriform plate and from there into the nasal lymphatics). Thus, many brain areas are exposed to and can be influenced by substances contained in the CSF. In this review we discuss the production and flow of the CSF, including the mechanisms involved in the regulation of its composition. In addition, the available evidence for the release of neuropeptides and other neuroactive substances into the CSF is reviewed, with particular attention to the selective effects of these on distant downstream receptive brain areas. As a conclusion we suggest that (1) the flowing CSF is involved in more than just nutrient and waste control, but is also used as a broadcasting system consisting of coordinated messages to a variety of nearby and distant brain areas; (2) this special form of volume transmission underlies changes in behavioral states.

The effect of a thoracic spinal block on fos expression in the lumbar spinal cord of the rat induced by a noxious electrical stimulus at the hindpaw.

BACKGROUND: Fos expression in the lumbar spinal cord, resulting from a noxious electrical stimulus at the hindpaw, is hypothesized to originate from three sources: direct sensory input of the noxious stimulus, local interactions in the spinal cord, and input of modulating signals from supraspinal regions. Our aim in this study was to discriminate among these sources by eliminating the supraspinal input. METHODS: Therefore, a spinal block was administered in male Wistar rats by administering a local anesthetic (bupivacaine) through an intrathecal catheter at the mid-thoracic level. This thoracic spinal block completely suppressed the noxious stimulation-induced withdrawal reflex that is normally elicited by electrical stimulus. Fos immunoreactivity (Fos-IR) was quantified in all laminae of the L4 segment of the spinal cord. RESULTS: Noxious stimulation resulted in a general and strong increase in Fos-IR in the ipsilateral dorsal horn, mainly in Laminae I, II, and V. Thoracic spinal block caused a remarkable increase in the amount of Fos-IR in Lamina V, but had no significant effect on the Fos-IR in Laminae I and II. CONCLUSIONS: The increase in Fos-IR in Lamina V may have resulted from the interruption of a pain-modulating descending mechanism from the brain. A known modulating descending mechanism is the serotonergic system, controlled by the periaqueductal gray. This system inhibits the neurons in the superficial laminae. Another nonserotonergic system originates in the anterior pretectal nucleus. The latter facilitates neurons in the superficial laminae, while neurons in Lamina V are inhibited. We conclude that both systems are probably involved in the observed effects of the peripheral noxious stimulation given in the present model.

Suppression of noxious-induced c-fos expression in the rat lumbar spinal cord by isoflurane alone or combined with fentanyl.

BACKGROUND: Although our understanding of nociceptive processing during anesthesia has increased greatly over the last decade, many patients still experience hyperalgesia and acute pain postoperatively. The noxious-induced withdrawal reflex (NIWR) model is specifically designed and validated to quantitatively study the reaction on painful, multimodal stimuli in animals under anesthetic conditions. Since the anesthetic mechanisms differ between inhaled anesthetics and opioids, we evaluated the differential effects of isoflurane and fentanyl on c-fos expression at the lumbar level as a measure of nociceptive information transfer during general anesthesia. METHODS: The experimental setup consisted of a randomized block design with four experimental groups: two light (3/4) minimum alveolar concentration (MAC) isoflurane anesthesia groups (unstimulated/NIWR-stimulated) and two NIWR-stimulated surgical anesthesia groups (1(1/2) MAC isoflurane anesthesia and (3/4) MAC isoflurane anesthesia combined with fentanyl 400-600 microg x kg(-1) x h(-1)). After 2 h of intermittent electrical stimulation of the hind paw of the rat, the number of Fos immunoreactive (Fos-IR) neurons in the dorsal horn was measured quantitatively. RESULTS: The main suppressive effects on lumbar c-fos expression of isoflurane were observed in the superficial lamina II (P = 0.02), whereas fentanyl showed the strongest effects in lamina V (P = 0.05). CONCLUSIONS: This study demonstrates that the NIWR model combined with spinal Fos-immunoreactivity is a suitable and useful model for evaluating the differential effects of inhaled anesthetics and opioids on nociceptive information transfer during general anesthesia.

Corticotropin-releasing factor, urocortin 1, and their receptors in the mouse spinal cord.

Corticotropin-releasing factor (CRF) and urocortin 1 (Ucn1) are involved in stress adaptation. CRF receptor 1 (CRF1) binds CRF and Ucn1 with similar high affinity, but CRF receptor 2 (CRF2) binds Ucn1 with higher affinity than CRF. We tested the hypothesis that in the spinal cord CRF and Ucn1 control peripheral components of the stress response, by assessing the distribution of CRF- and Ucn1-containing fibers, CRF1 and CRF2 mRNAs, and CRF receptor protein (CRFR) in the mouse spinal cord, by using immunofluorescence and in situ hybridization. CRF, Ucn1, and CRFR occurred throughout the spinal cord. CRF fibers predominated in laminae I, V-VII, and X of Rexed. Ucn1 fibers occurred mainly in laminae VII and X and occasionally in lamina IX. Both CRFR mRNAs occurred in all laminae except the superficial laminae of the dorsal horn, but they exhibited different distributions, CRF2 mRNA having a wider occurrence (laminae III-X) than CRF1 mRNA (laminae III-VIII). Double immunofluorescence indicated that CRF and Ucn1 fibers contacted CRFR-containing neurons, mainly in laminae VII and X. The strongest co-distribution of CRF1 and CRF2 mRNAs with CRF and Ucn1 fibers appeared in lamina VII. CRF2 mRNA predominated in lamina IX together with Ucn1, whereas CRF2 mRNA predominated in lamina X, where it had similar distributions with each ligand. In view of the lamina-specific and similar distributions of the two CRF receptor mRNAs with their ligands, we suggest that CRF1 and CRF2 are involved in peripheral stress adaptation processes, such as modulation of stress-induced analgesia and the mediation of visceral nociceptive information by CRF2.

Effects of acute and chronic apomorphine on sex behavior and copulation-induced neural activation in the male rat.

Apomorphine is a non-selective dopaminergic receptor agonist. Because of its pro-erectile effects, apomorphine is clinically used for treatment of erectile dysfunction. We investigated the effects of subcutaneous apomorphine administration (0.4 mg/kg rat) on sexual behavior and mating-induced Fos-expression following acute (day 1) or chronic apomorphine treatment (days 8 and 15) in sexually experienced male rats. Consistent facilitatory effects of apomorphine were observed in the reduced numbers of mounts and intromissions over time and an increased ejaculation frequency on day 1. The first post-ejaculatory interval, however, was lengthened, while other behavioral parameters were unaffected. Fos-immunoreactivity induced by acute apomorphine administration (barrel cortex, paraventricular hypothalamic nucleus, central amygdala and locus coeruleus) was strongly reduced after chronic administration. After mating, induction of Fos-immunoreactivity was observed in well-known areas like medial preoptic nucleus and the posterodorsal medial amygdaloid area. Apomorphine, however, reduced mating-induced Fos-immunoreactivity in the nucleus accumbens shell and prevented its occurrence in its core area. This remarkable apomorphine effect was not observed in any other brain area. We conclude that the behavioral (pro-erectile) effects of apomorphine are consistent over time, and that the diminished accumbens-Fos-immunoreactivity and the elongated post-ejaculatory interval may reflect a decreased response to remote cues from the estrus female.

Serotonin and the neurobiology of the ejaculatory threshold.

Disorders of the ejaculatory threshold, such as lifelong premature ejaculation, are fairly common in humans and can have a great impact on the quality of life. Research in humans and rats have indicated that increased serotonin levels in the central nervous system elevate the ejaculatory threshold, probably via 5-HT(1B) and 5-HT(2C) receptors, whereas depletion of serotonin decreases the ejaculatory threshold. 5-HT(1A) receptor activation strongly lowers the ejaculatory threshold, probably mediated by both the reduction of serotonin levels via presynaptic 5-HT(1A) receptors and yet unknown effects of postsynaptic 5-HT(1A) receptors. The present review attempts to integrate psychopharmacological data on serotonergic control over ejaculation with the knowledge of the neuroanatomical substrate of ejaculation, indicating the importance of the lumbosacral spinal cord, the nucleus paragigantocellularis, the lateral hypothalamic area and several other supraspinal areas. In addition, the gaps in our understanding of the role of serotonin in the ejaculatory threshold are discussed. Filling in those gaps might help to design specific drugs that alter the ejaculatory threshold, thereby alleviating ejaculatory disorders.

Distribution and expression of CRF receptor 1 and 2 mRNAs in the CRF over-expressing mouse brain.

Corticotropin-releasing factor (CRF) acts through CRF 1 and CRF 2 receptors (CRF1, CRF2). To test the hypothesis that CRF controls the expression of these receptors in a brain site- and receptor-type specific manner, we studied CRF1 mRNA and CRF2 mRNA expressions in mice with central CRF over-expression (CRF-OE) and using in situ hybridization. CRF1 and CRF2 mRNAs appear to be differentially distributed across the brain. The brain structures expressing the receptors are the same in wild-type (WT) and in CRF-OE mice. We therefore conclude that chronically elevated CRF does not induce or inhibit expression of these receptors in structures that normally do not or do, respectively, show these receptors. However, from counting cell body profiles positive for CRF1 and CRF2 mRNAs, clear differences appear in receptor expression between CRF-OE and WT mice, in a brain-structure-specific fashion. Whereas some structures do not differ, CRF-OE mice exhibit remarkably lower numbers of CRF1 mRNA-positive profiles in the subthalamic nucleus (-38.6%), globus pallidus (-31.5%), dorsal part of the lateral septum (-23.5%), substantia nigra (-22,8%), primary somatosensory cortex (-18.9%) and principal sensory nucleus V (-18.4%). Furthermore, a higher number of CRF2 mRNA-positive profiles are observed in the dorsal raphe nucleus (+32.2%). These data strongly indicate that central CRF over-expression in the mouse brain is associated with down-regulation of CRF1 mRNA and up-regulation of CRF2 mRNA in a brain-structure-specific way. On the basis of these results and the fact that CRF-OE mice reveal a number of physiological and autonomic symptoms that may be related to chronic stress, we suggest that CRF1 in the basal nuclei may be involved in disturbed information processing and that CRF2 in the dorsal raphe nucleus may play a role in mediating stress-induced release of serotonin by CRF.

Effects of chronic treatment with fluvoxamine and paroxetine during adolescence on serotonin-related behavior in adult male rats.

Selective Serotonin Reuptake Inhibitors (SSRIs) are designed to treat adults, but are increasingly prescribed for adolescents. SSRIs might cause permanent changes in serotonin-related behavior in adolescents, since their serotonergic system is still developing. Male Wistar rats were treated with paroxetine (15 mg/kg p.o.) or fluvoxamine (30 mg/kg p.o.) throughout adolescence. After a washout period their behavior in the elevated plus-maze, prepulse inhibition test, Forced swimming test and elevated T-maze were studied. In addition, the effects of the 5-HT(1A) receptor agonist 8-OH-DPAT on sexual behavior and lower lip retraction were measured. Paroxetine mildly inhibited weight gain during treatment. Both SSRIs caused a reduction in ejaculation frequency and in time spent on the open arm of the elevated plus-maze in adult rats. Fluvoxamine slightly increased avoidance latency in the elevated T-maze compared to paroxetine. No differences between the groups were found in the other tests. Apparently, chronic treatment with SSRIs during adolescence may cause mild changes in adult behavior.

Activation of a subset of lumbar spinothalamic neurons after copulatory behavior in male but not female rats.

The precise pathways that convey copulation-related information to forebrain regions activated during male and female sexual behavior are poorly understood. Previous work from our laboratory and others has demonstrated the existence of a spinothalamic pathway that is a candidate to relay information to these areas. This pathway originates from a population of spinothalamic neurons in the lumbar spinal cord containing several neuropeptides including galanin, located in laminas 7 and 10 of the lumbar segments 3 and 4. To investigate the involvement of these lumbar spinothalamic neurons in conveying copulation-related information, we tested the hypothesis that these cells are activated after ejaculation in male rats and vaginocervical stimulation in female rats. This was assessed using galanin or cholecystokinin as a marker for this subset of spinothalamic neurons and Fos-immunoreactivity as a marker for neuronal activation. The results demonstrated that activation of these spinothalamic neurons is triggered by stimuli associated with ejaculation. Fos induction was specifically associated with ejaculation, because mounts or intromissions did not trigger expression. Moreover, these spinothalamic neurons were not activated by vaginocervical stimulation in female rats. Spinothalamic neurons have generally been associated with signaling pain and temperature information. The present findings demonstrate that a specific subpopulation of spinothalamic neurons signals information associated with ejaculation.

Effects of chronic selective serotonin reuptake inhibitors on 8-OH-DPAT-induced facilitation of ejaculation in rats: comparison of fluvoxamine and paroxetine.

RATIONALE: Chronic treatment with selective serotonin reuptake inhibitors (SSRIs) can delay ejaculation in humans, but the extent of this effect differs between SSRIs. The involvement of 5-HT1A receptors is likely, since 5-HT1A receptor agonists accelerate ejaculation and chronic SSRI treatment is thought to desensitize 5-HT1A receptors. OBJECTIVES: This study was conducted to examine the effects of chronic pretreatment with the SSRIs fluvoxamine and paroxetine on the facilitation of ejaculation induced by the 5-HT1A receptor agonist 8-OH-DPAT. METHODS: Sexually experienced Wistar rats with normal ejaculatory behavior were treated for 22 days with vehicle, fluvoxamine (30 mg/kg/day), or paroxetine (10 or 20 mg/kg/day, p.o.). On day 22, rats received a challenge with saline or 8-OH-DPAT (0.4 mg/kg, s.c.). Sexual behavior was tested on days 1, 8, 15, and 22 of the SSRI-treatment. RESULTS: Treatment with both doses of paroxetine, but not fluvoxamine, delayed ejaculation. 8-OH-DPAT strongly accelerated ejaculation under vehicle conditions. Pretreatment with paroxetine reduced the effects of 8-OH-DPAT on ejaculation in a dose-dependent manner and more strongly than fluvoxamine. CONCLUSIONS: SSRIs affect 5-HT1A receptors involved in ejaculation. The degree to which this occurs, with paroxetine exerting a stronger effect than fluvoxamine, might determine the extent of SSRI-induced delayed ejaculation.

Opioid peptides, CRF, and urocortin in cerebrospinal fluid-contacting neurons in Xenopus laevis.

The presence of the opioids, beta-endorphin, met-enkephalin, and endomorphin, and of corticotropin-releasing factor (CRF) and the CRF family member, urocortin (Ucn), is described in cerebrospinal fluid-contacting neurons in the brain of the amphibian, Xenopus laevis.

Do similar neural systems subserve aggressive and sexual behaviour in male rats? Insights from c-Fos and pharmacological studies.

It is a common belief that male aggressive and sexual behaviour share many of the underlying neurobiological, neurological, pharmacological and neuroendocrine mechanisms. Therefore, we studied brain activation patterns in male rat after performance of aggressive and sexual behaviour and compared serotonergic pharmacology in the same paradigms to delineate possible similarities and differences. Patterns of Fos-immunoreactivity induced by aggressive and sexual encounters of Wild-type male Brown Norway rats were studied to localise the commonly activated (functionally shared) parts of the circuitry, and the specific (functionally different) parts of the neuronal circuitry. Some brain areas (caudal medial preoptic area and medial amygdala) were commonly activated, but other areas (e.g. posterodorsal parts of the medial amygdala, rostral preoptic and premammillary hypothalamus) showed remarkably specific differences in neural activation. 5-HT(1A) receptor agonists inhibit aggressive, but stimulate male sexual behaviour, whereas 5-HT(1B) receptor agonists inhibit both types of behaviour. Selective serotonin reuptake inhibitors share comparable inhibitory effects in aggression and sexual behaviour, although only at relatively high doses. We propose that separate hard-wired neural systems exist in the brain for aggressive and sexual behaviours, modulated via hierarchically 'higher-level' brain areas that are involved in the integration (gating) of the behavioural outcome of an organism.

Citalopram combined with WAY 100635 inhibits ejaculation and ejaculation-related Fos immunoreactivity.

The role of 5-HT (5-hydroxytryptamine, 5-HT)(1A) receptor activation in the sexual side-effects, in particular delayed ejaculation, of selective serotonin reuptake inhibitors (SSRIs) was studied. Male Wistar rats were treated for 15 days with vehicle, the SSRI citalopram (10 mg/kg/day p.o.), the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl) cyclohexane carboxamide 3HCL (WAY 100635, 0.1 mg/kg/ day s.c.), or both drugs combined. Sexual behavior was assessed weekly. One h after the last sexual behavior test, rat brains were processed for Fos-immunohistochemistry. Acute and chronic citalopram mildly inhibited ejaculation, which was strongly augmented by co-administration of WAY 100635. WAY 100635 alone did not alter sexual behavior. Brain sites associated with ejaculation showed reduced Fos-immunoreactivity in rats treated with both citalopram and WAY 100635. Citalopram reduced Fos-immunoreactivity in the arcuate hypothalamic nucleus, an area that might link serotonergic neurotransmission to ejaculation.

A single exposure to novelty differentially affects the accumbal dopaminergic system of apomorphine-susceptible and apomorphine-unsusceptible rats.

Individual differences in responses to mild, acute stressors in laboratory animals have commonly been observed in behavioural tests and at the level of hypothalamic-pituitary-adrenal axis responses. These differences are associated with dopamine transmission in the nucleus accumbens. Although the effect of mild stressors on dopamine transmission has been studied with microdialysis, it has not been studied at the level of the catecholaminergic network in the nucleus accumbens. In this study we have used microdialysis to measure extracellular concentrations of dopamine in vivo and immunocytochemistry for the enzyme tyrosine hydroxylase to assess the effect of a single exposure to novelty on the neurochemistry of the nucleus acc umbens in apomorphine-susceptible and apomorphine-unsusceptible rats. These rats are a valid animal model for studying individual differences in responses to environmental stressors and drugs of abuse. We demonstrated that a mild stressor like novelty increased the extracellular concentration of dopamine in the nucleus accumbens in apomorphine-susceptible rats to a larger and longer-lasting degree than in apomorphine-unsusceptible rats. Furthermore we demonstrated that novelty increased the tyrosine hydroxylase-immunoreactive fibre network in the nucleus accumbens shell of apomorphine-susceptible rats, which are rats that are particularly reactive to stressors, but not in the shell of apomorphine-unsusceptible rats, which are rats that are relatively stress-resistant. In conclusion, we have shown that the accumbal dopaminergic system of apomorphine-susceptible rats is more sensitive to an environmental stressor than that of apomorphine-unsusceptible rats. Combined with the fact that these animals also differ in their sensitivity to drugs of abuse, which are known to affect the dopaminergic system, these data provide a solid basis for further studying the differences in the dopaminergic responsiveness to drugs of abuse between apomorphine-susceptible and apomorphine-unsusceptible rats.

The effects of beta-endorphin: state change modification.

Beta-endorphin (ß-END) is an opioid neuropeptide which has an important role in the development of hypotheses concerning the non-synaptic or paracrine communication of brain messages. This kind of communication between neurons has been designated volume transmission (VT) to differentiate it clearly from synaptic communication. VT occurs over short as well as long distances via the extracellular space in the brain, as well as via the cerebrospinal fluid (CSF) flowing through the ventricular spaces inside the brain and the arachnoid space surrounding the central nervous system (CNS). To understand how ß-END can have specific behavioral effects, we use the notion behavioral state, inspired by the concept of machine state, coming from Turing (Proc London Math Soc, Series 2,42:230-265, 1937). In section 1.4 the sequential organization of male rat behavior is explained showing that an animal is not free to switch into another state at any given moment. Funneling-constraints restrict the number of possible behavioral transitions in specific phases while at other moments in the sequence the transition to other behavioral states is almost completely open. The effects of ß-END on behaviors like food intake and sexual behavior, and the mechanisms involved in reward, meditation and pain control are discussed in detail. The effects on the sequential organization of behavior and on state transitions dominate the description of these effects.

HPA axis dysregulation in mice overexpressing corticotropin releasing hormone.

BACKGROUND: Hypersecretion of corticotropin-releasing hormone (CRH) in the brain has been implicated in stress-related human pathologies. We developed a transgenic mouse line overexpressing CRH (CRH-OE) exclusively in neural tissues to assess the effect of long-term CRH overproduction on regulation of the hypothalamic-pituitary-adrenal (HPA) axis. METHODS: Male transgenic CRH-OE(2122) mice on a C57BL/6J background were used. Littermate wildtype mice served as control animals. Basal plasma corticotropin and corticosterone concentrations were measured, and adrenal gland weight was determined. A dexamethasone suppression test measured the effects of long-term CRH hypersecretion on negative feedback control. Additionally, we measured plasma corticosterone concentrations in reaction to stress. RESULTS: CRH-OE(2122) mice showed elevated basal plasma corticosterone concentrations, hypertrophy of the adrenal gland, and dexamethasone nonsuppression. Basal plasma ACTH concentrations of wildtype and CRH-OE(2122) mice did not differ significantly. In reaction to stress, CRH-OE(2122) mice showed a normal corticosterone response. CONCLUSIONS: The HPA axis abnormalities observed in CRH-OE(2122) mice suggest that long-term hypersecretion of CRH in the brain can be a main cause of HPA axis dysregulation. The alterations in HPA axis regulation are reminiscent of changes reported in major depressive disorder. As such, these CRH -OE(2122) mice may model the neuroendocrine changes observed in major depressive disorder.

Parvocellular subparafascicular thalamic nucleus in the rat: anatomical and functional compartmentalization.

The parvocellular subparafascicular thalamic nucleus (SPFp) is located in the posterior thalamus, consists of horizontally oriented cells, and extends from rostromedial to caudolateral, fusing with the posterior intralaminar nucleus and the peripeduncular nucleus. The present study demonstrates a chemoarchitechtonic and functional parcellation of the rat SPFp. Analysis of the distributions of the neuropeptides galanin, calcitonin gene related peptide (CGRP), substance P, and calbindin revealed the existence of a medial and lateral subdivision within SPFp, and a possible intermediate subdivision. The medial subdivision contains a dense population of galanin-immunoreactive fibers, originating from galanin neurons in the lumbosacral spinal cord. In contrast, the lateral subdivision contains CGRP-positive fibers and neurons. The presence of substance P and calbindin immunoreactivity throughout the entire nucleus suggests that these are separate subdivisions of SPFp, rather than different subnuclei. The present study also investigated the functional association of the separate subdivisions of SPFp for male and female rat sexual behavior. In the medial subdivision, Fos-positive neurons were activated in males by display of ejaculation and in females by vaginocervical stimulation. Thus, Fos induction in medial SPFp appears to reflect processing of inputs related to those events. In contrast, sexual behavior did not induce Fos in the lateral SPFp. Taken together, the present results indicate the existence of separate subdivisions in SPFp that are involved in different behavioral functions. The medial SPFp may process inputs important for sexual behavior, whereas the lateral SPFp may be involved in convergence of auditory and nociceptive inputs important for conditioned fear responses.

Afferent connections of the parvocellular subparafascicular thalamic nucleus in the rat: evidence for functional subdivisions.

The parvocellular subparafascicular nucleus of the thalamus (SPFp) consists of separate subdivisions, i.e., a medial portion containing galanin-immunoreactive (-IR) axons and a lateral portion containing calcitonin gene related peptide (CGRP)-IR neurons and fibers. These subdivisions appear to have distinct functional roles. In particular, ejaculation-induced Fos expression is expressed in the medial SPFp. Hence, it was hypothesized that medial SPFp is involved in relay of copulation-related information. In contrast, lateral SPFp is involved in the processing of auditory and visual signals involved in fear-conditioned responses. Here we tested the hypothesis that medial and lateral subdivisions of SPFp receive different sets of afferents and that these differences contribute to the separate functional roles of the two subdivisions. Inputs to medial and lateral SPFp were identified following injections of FG restricted to either division in male rats. The medial SPFp receives unique inputs from lumbar spinothalamic cells and brain regions involved in processing of visceral stimuli, supporting the hypothesis that the medial SPFp is involved in the relay of genitosensory information critical for the expression of male sexual behavior. The afferents of the lateral SPFp include brain regions involved in processing of visual and auditory signals and support a role for this subdivision in relay of visual and auditory information. Thus, the two subdivisions of SPFp are anatomically and functionally distinctive.

The selective serotonin re-uptake inhibitors fluvoxamine and paroxetine differ in sexual inhibitory effects after chronic treatment.

RATIONALE: The selective serotonin re-uptake inhibitors (SSRIs) delay orgasm and ejaculation in men. In men with rapid ejaculation it was shown that, of the SSRIs, paroxetine exerted the strongest delay in ejaculation and fluvoxamine the weakest. OBJECTIVES: In the present study, we compared the acute and chronic effects of fluvoxamine and paroxetine on sexual behavior in the male rat in order to compare their differential inhibitory effects on sexual behavior. METHODS: During a 4-week period, 48 male Wistar rats, selected on the basis of their sexual performance, were repeatedly tested for sexual behavior. All male rats received vehicle (saline, n=12), fluvoxamine (30 mg/kg, n=12), or paroxetine (10 mg/kg, n=12) daily for 2 weeks. Sexual behavioral tests were performed on days 1 (acute), 7, and 14. RESULTS: After acute oral administration, fluvoxamine and paroxetine did not inhibit sexual behavior. After 7 days and 14 days treatment, fluvoxamine mildly inhibited certain parameters of sexual behavior but ejaculation was never delayed. In contrast, paroxetine, after 7 days and particularly after 14 days treatment, strongly inhibited sexual behavior, including ejaculation. CONCLUSIONS: These results strongly concur with clinical data, suggesting that paroxetine, but not fluvoxamine, delays ejaculation. Because fluvoxamine does not delay ejaculation it may serve as an optimal treatment for depressive illness when sexual side effects, such as a delayed ejaculation, are undesired. The mechanisms whereby paroxetine and fluvoxamine, both being selective serotonin uptake inhibitors, differentially inhibit sexual behavior are unclear.