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Lique M Coolen

Publications and source records attributed to Lique M Coolen.

At least 19 recordsLinked to original sources
PubMed2006

Neurons containing tuberoinfundibular peptide of 39 residues are activated following male sexual behavior.

Tuberoinfundibular peptide of 39 residues (TIP39)-immunoreactive (IR) neurons are present in the medial subdivision of the parvocellular subparafascicular thalamic nucleus (mSPFp) where ejaculation-specific Fos expression is localized. The mSPFp is reciprocally connected to the medial preoptic area (MPOA), bed nucleus of the stria terminalis (BNST) and the medial nucleus of the amygdala (Me), all of which are critical for the regulation of male sexual behavior. The mSPFp also receives galanin and enkephalin containing projections from a region in the lumbar spinal cord, thought to be a central ejaculation center. Therefore, we hypothesized that TIP39 neurons in the mSPFp may be part of the neuronal circuitry activated by male sexual behavior. To test this hypothesis, we examined induction of Fos in TIP39 containing neurons in the mSPFp following male sexual behavior. Mating-induced Fos expression was evaluated in sexually experienced male rats under four experimental conditions: animals that (1) remained in their home cage without any interaction with females, (2) interacted with stimulus females and displayed intromission without ejaculation, (3) displayed one ejaculation, or (4) displayed 2 ejaculations. We found that Fos was induced in TIP39-IR neurons in the mSPFp in male rats following ejaculation but much less so following intromission without ejaculation. This suggests that TIP39-IR neurons in the mSPFp are part of the afferent circuits that process genital-somatosensory information related to ejaculation, and which contribute to mating and mating-induced changes in reproductive behavior.

Amygdala↗
PubMed2006

Morphological plasticity in the neural circuitry responsible for seasonal breeding in the ewe.

An increase in the response of GnRH neurons to estrogen negative feedback is responsible for seasonal anestrus in the ewe, but the underlying neural mechanisms remain largely unknown. Neural plasticity may play an important role because the density of synaptic input to GnRH neurons changes with seasons. Moreover, the transition from breeding to anestrous season requires thyroid hormones, which are also required for neuronal development. In the first experiment, we examined whether the decrease in synapses on GnRH neurons is critical for the transition to anestrus by comparing synaptic input in thyroidectomized and thyroid-intact controls, using electron microscopic analysis. Thyroidectomized ewes remained in the breeding season, but the number of synaptic contacts on their GnRH cells was not different from those in thyroid-intact ewes that were anestrus. The next experiment tested whether there was a seasonal change in morphology of the A15 dopaminergic neurons that mediate estrogen negative feedback during anestrus by analyzing synapsin-positive close contacts onto A15 neurons with confocal microscopy. There was a 2-fold increase in these close contacts onto dendrites of A15 neurons in anestrus and a corresponding increase in the length of A15 dendrites at this time of year. The increase in dendritic length was blocked by thyroidectomy, but this procedure did not significantly affect synaptic input to A15 neurons. These results provide initial evidence that the seasonal change in synapses on GnRH neurons is not sufficient for the transition into anestrus but that plasticity of the A15 dopaminergic neurons mediating estrogen negative feedback may contribute to this seasonal alteration.

Anestrus↗
PubMed2006

Risperidone pretreatment prevents elevated locomotor activity following neonatal hippocampal lesions.

Long-standing behavioral abnormalities emerge after puberty in rats following neonatal hippocampal lesion, providing a developmental model of abnormal rat behavior that may have predictive validity in identifying compounds effective in treating symptoms of schizophrenia. We sought to test the predictive validity of the neonatal hippocampal lesion model in identifying preventive treatment for first-episode psychosis. We determined the effect of risperidone, recently studied for prevention of first-episode psychosis, on the development of elevated locomotor activity following neonatal hippocampal lesions. Rat pups received hippocampal or sham lesions on postnatal day 7, followed by treatment with risperidone or vehicle from postnatal days 35 to 56. Locomotor activity in response to novelty, amphetamine, and nocturnal locomotion were determined on postnatal day 57. Low-dose risperidone (45 microg/kg) pretreatment prevented elevated locomotor activity in some, but not all, of the behavioral tasks following neonatal hippocampal lesions. In contrast, higher risperidone pretreatment was less effective in preventing elevated locomotor activity following neonatal hippocampal lesions. Because low risperidone dosages were also found to be effective in preventing first-episode psychosis in human studies, these data support the predictive validity of the hippocampal lesion model in identifying medications for prevention of first-episode psychosis. Additionally, these data support the use of low-dose risperidone in psychosis prevention, and suggest the possibility that higher risperidone doses could be less effective in this application.

Amphetamine↗
PubMed2005

Neural control of ejaculation.

Ejaculation is the most reinforcing component of sexual behavior. However, the neural substrates mediating ejaculation and processing ejaculation-related signals remain poorly understood. We review the current understanding of central control of ejaculation. Specifically, the recent identification of a candidate spinothalamic pathway involved in relay of ejaculation-specific signals is discussed. In addition, the discovery of a neural population of lumbar interneurons playing an pivotal role in expression of ejaculation is reviewed.

Animals↗
PubMed2005

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.

Aggression↗
PubMed2005

Spinal cord control of ejaculation.

Ejaculation is a reflex mediated by a spinal control center, referred to as a spinal ejaculation generator. During intercourse, the spinal ejaculation generator integrates the sensory inputs that are necessary to trigger ejaculation. At the time of ejaculation, it coordinates the sympathetic, parasympathetic, and somatic outflow to induce the two phases of ejaculation, i.e. emission and expulsion. It also provides the brain with signals related to the occurrence of ejaculation. Experimental and clinical data evidenced that these functions were devoted to neurons located in the lumbosacral cord. We recently characterized a population of spinothalamic neurons in the lumbar spinal cord of male rats (LSt cells) that constitutes an integral part of the spinal ejaculation generator. LSt cells send projections to the autonomic nuclei and motoneurons involved in the emission and expulsion phase, and they receive sensory projections from the pelvis. LSt cells are activated with ejaculation, but not following other components of sexual behavior, and lesions of LSt cells completely ablate ejaculatory function. These data support a pivotal role for the LSt cells in the control of ejaculation.

Animals↗
PubMed2004

Central regulation of ejaculation.

Ejaculation is a reflex mediated by a spinal control center, referred to as a spinal ejaculation generator. This spinal ejaculation generator coordinates sympathetic, parasympathetic and motor outflow to induce the two phases of ejaculation, i.e., emission and expulsion. In addition, the spinal ejaculation generator integrates this outflow with inputs that are related to the summation of sexual activity prior to ejaculation that are required to trigger ejaculation. Recently, a group of spinothalamic neurons in the lumbar spinal cord (LSt cells) were demonstrated to comprise an integral part of the spinal ejaculation generator. Specifically, lesions of LSt cells completely ablate ejaculatory function. Moreover, LSt cells are activated following ejaculation, but not following other components of sexual behavior. Furthermore, based on their relationship with autonomic nuclei, motoneurons and genital sensory inputs, LSt cells are also in the ideal anatomical position to integrate sensory inputs and autonomic and motor outflow. Additionally, the spinal ejaculation generator is under inhibitory and excitatory influence of supraspinal sites, including the nucleus paragigantocellularis (nPGi), the paraventricular nucleus of the hypothalamus (PVN) and the medial preoptic area (MPOA). Finally, sensory information related to ejaculation is processed in the spinal cord and brain, possibly contributing to the rewarding properties of ejaculation. One candidate pathway for relay of ejaculation-related cues consists of LSt cells and their projections to the parvocellular subparafascicular thalamic nucleus. Moreover, neural activation specifically related to ejaculation is observed in the brain and may reflect of processing of ejaculation-related sensory cues.

Animals↗
PubMed2004

Neural system-enriched gene expression: relationship to biological pathways and neurological diseases.

To understand the commitment of the genome to nervous system differentiation and function, we sought to compare nervous system gene expression to that of a wide variety of other tissues by gene expression database construction and mining. Gene expression profiles of 10 different adult nervous tissues were compared with that of 72 other tissues. Using ANOVA, we identified 1,361 genes whose expression was higher in the nervous system than other organs and, separately, 600 genes whose expression was at least threefold higher in one or more regions of the nervous system compared with their median expression across all organs. Of the 600 genes, 381 overlapped with the 1,361-gene list. Limited in situ gene expression analysis confirmed that identified genes did represent nervous system-enriched gene expression, and we therefore sought to evaluate the validity and significance of these top-ranked nervous system genes using known gene literature and gene ontology categorization criteria. Diverse functional categories were present in the 381 genes, including genes involved in intracellular signaling, cytoskeleton structure and function, enzymes, RNA metabolism and transcription, membrane proteins, as well as cell differentiation, death, proliferation, and division. We searched existing public sites and identified 110 known genes related to mental retardation, neurological disease, and neurodegeneration. Twenty-one of the 381 genes were within the 110-gene list, compared with a random expectation of 5. This suggests that the 381 genes provide a candidate set for further analyses in neurological and psychiatric disease studies and that as a field, we are as yet, far from a large-scale understanding of the genes that are critical for nervous system structure and function. Together, our data indicate the power of profiling an individual biologic system in a multisystem context to gain insight into the genomic basis of its structure and function.

Animals↗
PubMed2004

Differential effects of adrenalectomy on melanin-concentrating hormone and orexin A.

Removal of glucocorticoids by adrenalectomy (ADX) reduces food intake and body weight in rodents and prevents excessive weight gain in many genetic and dietary models of obesity. Glucocorticoids play a key role to promote positive energy balance in normal and pathological conditions, at least in part, by altering the sensitivity to hypothalamic peptides. The hyperphagia after central neuropeptide Y administration, for example, is attenuated by ADX, and there is evidence that glucocorticoids influence both MCH and orexin A activity. In the present study, feeding responses to third ventricular MCH and orexin A were measured in rats after bilateral ADX or sham surgery. ADX rats were significantly less sensitive to the orexigenic action of third ventricular MCH, whereas orexin A-induced hyperphagia was unaffected. Replacement of corticosterone in the drinking water of ADX rats reversed the effects of ADX on MCH sensitivity. Although we found significant populations of glucocorticoid receptors in the lateral hypothalamus, none were colocalized with either MCH or orexin A-containing cell bodies. Furthermore, whereas ADX significantly reduced hypothalamic MCH and orexin gene expression, this could not be restored by glucocorticoids in the drinking water. Collectively, the present data suggest that glucocorticoids may promote food intake in part by potentiating the orexigenic actions of MCH without affecting the actions of orexin A and that glucocorticoids act indirectly to influence the effects of MCH on food intake.

Adrenalectomy↗
PubMed2004

Evidence that dynorphin plays a major role in mediating progesterone negative feedback on gonadotropin-releasing hormone neurons in sheep.

Endogenous opioid peptides (EOP) mediate progesterone-negative feedback in many species, but the specific EOP systems involved remain unresolved. We first addressed this question in sheep by determining the role of different EOP receptor subtypes in the medial basal hypothalamus (MBH) and preoptic area (POA). Local administration of EOP receptor antagonists to luteal phase ewes indicated that kappa-, but not micro- or delta-, receptors mediate the inhibition of LH secretion in the MBH. In contrast, both kappa- and micro-, but not delta-receptor, antagonists increased LH pulse frequency when placed in the POA. We next examined close appositions between dynorphin (kappa ligand) and beta-endorphin (micro ligand) containing varicosities and GnRH perikarya in luteal phase ewes using dual immunocytochemistry and light microscopy. Approximately 90% of MBH GnRH neurons had close associations by dynorphin-containing varicosities, but only 40-50% of GnRH perikarya elsewhere had such close associations. In contrast, the percentage of beta-endorphinergic varicosities close to GnRH neurons was similar among all regions. Electron microscopic analysis demonstrated both dynorphinergic synapses and beta-endorphinergic synapses onto GnRH perikarya. These and other data lead to the hypothesis that dynorphin neurons play a major role in progesterone-negative feedback in the ewe and that this inhibition may be exerted directly on GnRH perikarya within the MBH, whereas dynorphin and beta-endorphin input to GnRH neurons in the POA provide redundancy to this system or are involved in other actions of progesterone or estradiol in the control of the GnRH surge.

Animals↗
PubMed2004

The premammillary hypothalamic area of the ewe: anatomical characterization of a melatonin target area mediating seasonal reproduction.

Recent evidence suggests that the ovine premammillary hypothalamic area (PMH) is an important target for the pineal hormone, melatonin, and its role in seasonal reproduction. In rodents, the PMH is a complex region consisting of several cell groups with differing neurochemical content and anatomical connections. Therefore, to obtain a better understanding of the potential neural targets for melatonin in this area of the sheep brain, we have undertaken a detailed anatomical characterization of the PMH, including its nuclear divisions and the location of neuropeptide/neurotransmitter cells within them. By combining immunocytochemistry for NeuN, a neuronal marker, with Nissl staining in anestrous, ovariectomized, estradiol-treated ewes, we identified three nuclei within the PMH: a caudal continuation of the hypothalamic arcuate nucleus (cARC), the ventral division of the premammillary nucleus (PMv), and the ventral tuberomammillary nucleus (TMv). The cARC contained neurons that were immunoreactive for tyrosine hydroxylase, dynorphin, estrogen receptor alpha, cocaine- and amphetamine-regulated transcript peptide (CART), and nitric oxide synthase (NOS). The PMv was also characterized by the presence of cells that contained NOS and CART, although the size of these cells was larger than that of their corresponding phenotype in the cARC. By contrast, in the TMv, of the markers examined in the present study, only fibers immunoreactive for orexin were seen. Thus, the ovine PMH is a heterogeneous region comprised of three subdivisions, each with distinct morphological and neurochemical characteristics. This anatomical map of the PMH provides a basis for future studies to determine the functional contribution of each component to the influence of melatonin on seasonal reproduction.

Animals↗
PubMed2004

Involvement of nitric oxide in sexual learning via action in the medial preoptic area: theoretical comment on Lagoda et al. (2004).

Repeated exposure to female-related stimuli causes functional alterations in the neural circuitry mediating male rat sexual behavior. In a study published in the current issue of this journal, G. M. Lagoda, J. W. Muschamp, A. Vigdorchik, and E. M. Hull (2004) provide interesting new evidence as to the mechanisms responsible for this effect, namely via activity of nitric oxide (NO) in the medial preoptic area. Given the history of NO in mediating neural plasticity in other systems, the results point to common mechanisms of plasticity between the processes underlying acquisition of sexual experience and those involved in learning and memory.

Animals↗
PubMed2004

Sexual behavior and sex-associated environmental cues activate the mesolimbic system in male rats.

The mesolimbic system plays an important role in the regulation of both pathological behaviors such as drug addiction and normal motivated behaviors such as sexual behavior. The present study investigated the mechanism by which this system is endogenously activated during sexual behavior. Specifically, the effects of sexual experience and sex-related environmental cues on the activation of several components of the mesolimbic system were studied. The mesolimbic system consists of a dopaminergic projection from the ventral tegmental area (VTA) to the nucleus accumbens (NAc). Previous studies suggest that these neurons are under tonic inhibition by local GABA interneurons, which are in turn modulated by mu opioid receptor (MOR) ligands. To test the hypothesis that opioids are acting in the VTA during sexual behavior, visualization of MOR internalization in VTA was used as a marker for ligand-induced activation of the receptor. Significant increases in MOR internalization were observed following copulation or exposure to sex-related environmental cues. The next goal was to determine if sexual behavior activates dopamine neurons in the VTA, using tyrosine hydroxylase as a marker for dopaminergic neurons and Fos-immunoreactivity as a marker for neuronal activation. Significant increases in the percentage of activated dopaminergic neurons were observed following copulation or exposure to sex-related environmental cues. In addition, mating and sex-related cues activated a large population of nondopaminergic neurons in VTA as well as neurons in both the NAc Core and Shell. Taken together, our results provide functional neuroanatomical evidence that the mesolimbic system is activated by both sexual behavior and exposure to sex-related environmental cues.

Animals↗
PubMed2003

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.

Afferent Pathways↗
PubMed2003

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.

Animals↗
PubMed2003

Altered behavioral response to dopamine D3 receptor agonists 7-OH-DPAT and PD 128907 following repetitive amphetamine administration.

Behavioral sensitization, the progressive and enduring enhancement of certain behaviors following repetitive drug use, is mediated in part by dopaminergic pathways. Increased locomotor response to drug treatment, a sensitizable behavior, is modulated by an opposing balance of dopamine receptor subtypes, with D1/D2 dopamine receptor stimulation increasing and D3 dopamine receptor activation inhibiting amphetamine-induced locomotion. We hypothesize that tolerance of D3 receptor locomotor inhibition contributes to behavioral sensitization. In order to test the hypothesis that expression of behavioral sensitization results in part from release of D3 receptor-mediated inhibition, thereby resulting in decreased response to D3 receptor agonists, we examined the effect of repetitive amphetamine administration on the behavioral response to the D3 receptor preferring agonists 7-OH-DPAT and PD 128907. D3-selective effects have recently been described for both drugs at a low dose. At 1 week following completion of a repetitive treatment regimen, amphetamine-pretreated rats displayed a decreased response to D3-selective doses of both 7-OH-DPAT and PD 128907, when compared to animals receiving saline pretreatment. Moreover, in addition to the quantitative alteration in response, there was a change in the inter-relation between response to amphetamine and D3 agonist. A highly significant inverse relation between locomotor inhibitory response to PD 128907 and the locomotor-stimulant response to amphetamine was observed prior to amphetamine treatment. In contrast, 10 days following repetitive amphetamine treatment, the relation between response to PD 128907 and amphetamine was not detected. The observed behavioral alteration could not be accounted for by changes in D3 receptor binding in ventral striatum. These findings suggest a persistent release of D3 receptor-mediated inhibitory influence contributes to the expression of behavioral sensitization to amphetamine.

Amphetamine↗
PubMed2003

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.

8-Hydroxy-2-(di-n-propylamino)tetralin↗