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Role of the medial preoptic area in thermal preference of rats.

This study was conducted to find out whether the medial preoptic area (mPOA) plays a role in the selection of ambient temperature by rats. Adult male Wistar rats were kept in an environmental chamber having three interconnected compartments, maintained at three different temperatures (18 degrees, 24 degrees and 30 degrees C) in which the animals could move freely from one compartment to the other. Normal rats preferred to stay at the chamber maintained at 24 degrees C for most of the time, during day and night. The temperature preference shifted to 30 degrees C after the mPOA of these rats had been lesioned by local administration of 5 micrograms of N-methyl D-aspartic acid (NMDA) in 0.2 microliter distilled water. The results of the study suggest that the mPOA acts as a fine tuning center for homeostatic regulation of thermal balance, including selection of appropriate thermal environment. It is proposed that after the mPOA lesion, the animal cannot assess properly the energy status of the body and thereby prefers a higher ambient temperature.

Animals↗

Differential regulation of female rat olfactory preference and copulatory pacing by the lateral septum and medial preoptic area.

We examined the effect of bilateral radiofrequency lesions in the lateral septum (LS) or medial preoptic area (MPOA) on olfactory preference (time spent sniffing odors derived from either a stud or castrated male) and pacing behavior (paracopulatory behavior in a cage with a compartment inaccessible to males) in ovariectomized rats following different hormonal regimes. Sham-operated and LS-lesioned females, but not MPOA-lesioned females, preferred odors from the stud males to the castrated males. MPOA lesions significantly decreased total nose-poking time, compared to that of sham-operated females. When mounted by stud males, both LS- and MPOA-lesioned females showed significantly higher lordosis quotients than sham-operated females. On the other hand, LS-lesioned females spent a significantly longer time in the male compartment, and stayed with the males even after they were mounted. These results suggest that the LS and MPOA play different roles in the sociosexual activity in female rats, and that the two regions exert an inhibitory influence on lordosis.

Analysis of Variance↗

Plasma LH rises rapidly following mating in hypogonadal female mice with preoptic area (POA) brain grafts.

Hypogonadal female mice, genetically deficient in gonadotropin releasing hormone (GnRH), respond to preoptic area (POA) grafts obtained from normal fetal or neonatal mice with increased gonadotropin levels, ovarian and uterine development and continual vaginal estrus rather than spontaneous ovulatory cyclicity. Previous studies showed that such mice became pregnant following one overnight pairing with a normal male, indicating reflex ovulation. The present study evaluated plasma LH concentrations in relation to mating. Plasma LH levels in the hpg females with POA grafts were significantly elevated 10 min following the male partner's ejaculation, but were no different than baseline at 30, 60 or 120 min following the male's ejaculation. The post-copulatory plasma LH levels of 3.0 +/- 0.6 ng/ml (mean +/- S.E.M.) were considerably lower than the proestrous LH surge seen in the normal females in the colony (16.8 +/- 4.8 ng/ml), but in at least 4 of 10 hpg mice the levels were sufficient to induce ovulation as proved by pregnancy following this single mating. Grafts contained GnRH-reactive cells and fibers that projected to the median eminence of the host brains.

Animals↗

Semi-quantitative analysis of the effects of estrogen on CGRP- and methionine-enkephalin-immunoreactivity in the periventricular preoptic nucleus and the medial preoptic area of female rats.

The effects of 17 beta-estradiol (E2) on calcitonin gene-related peptide (CGRP)- and methionine-enkephalin (Met-Enk)-immunoreactive (IR) nerve fibers in the periventricular preoptic nucleus (Pe) and the medial preoptic area, including the medial preoptic nucleus (MPN), of the female rat were studied semi-quantitatively by using a computer-based image analysis system. The area occupied by CGRP- and Met-Enk-IR fibers was significantly increased in the Pe and the MPN after 28-day exposure to E2. Computer-based analysis of CGRP- and Met-Enk-IR fibers in an area of 50-microns intervals from the wall of the third ventricle showed a low flat histogram pattern in ovariectomized rats, but E2 treatment caused a diphasic pattern, corresponding to the Pe and the MPN, respectively. Since the Pe and the MPN contain a high population of estrogen receptors, it is suggested that E2 may have an influence on the neuronal configuration of afferent fibers to these areas.

Animals↗

Selective regulation of glutamic decarboxylase isoform 65, but not isoform 67, in the bed nucleus of the stria terminalis and the preoptic area of the ewe brain across the estrous cycle.

gamma-Aminobutyric acid neurons in the preoptic area (POA) of the brain may regulate GnRH neurons. The level of expression of two isoforms (65 and 67) of glutamic acid decarboxylase (GAD) in the ewe brain was determined across the estrous cycle by in situ hybridization. GAD mRNA expression (cell number and silver grains/cell) was examined in the subdivisions of the bed nucleus of stria terminalis (BnST), in the diagonal band of Broca, and the POA. The number of cells expressing GAD(65) and GAD(67) mRNA did not change across the cycle. Within the rostro-dorsal BnST, the number of silver grains/cell for GAD(65) mRNA was lower in the follicular phase than the luteal phase or at estrus. In the rostro-lateral division, expression was lower in the follicular phase. In the POA, the number of silver grains/cell for GAD(65) mRNA was lower at estrus than during the luteal phase. The number of silver grains/cell for GAD(67) mRNA did not change across the estrous cycle. GAD(65) is thought to be the active enzyme during periods of high demand of GABA and our results are consistent with the GABA neurons of BnST being most active during the luteal phase of the estrous cycle.

Animals↗

Preoptic area lesions disrupt prolactin-induced parental feeding behavior in ring doves.

The role of the preoptic area (POA) in mediating PRL-induced parental responsiveness toward young was investigated in nonbreeding-doves with previous breeding experience. Birds received microinjections of the axon-sparing excitotoxin ibotenic acid to destroy neuronal cell bodies in the POA. Sham-lesioned controls received POA injections of vehicle. Upon recovery, birds received subcutaneous injections of ovine PRL for 7 days, followed by a 2.5-hr test with a foster squab to assess parental responsiveness. Lesioned doves displayed significantly fewer parental feeding invitations, parental regurgitation feeding bouts, and total regurgitation movements than did sham-lesioned animals. As a result, nestlings given to sham-lesioned birds gained significantly more weight than those given to lesioned birds. A significant negative correlation was obtained between the extent of POA damage induced by ibotenic acid infusion and the amount of parental behavior displayed by lesioned animals. These deficits in parental behavior were apparently a selective effect of POA damage because another PRL-mediated behavior, hyperphagia, was unaffected. The results suggest that the POA is an important component of the neural circuitry underlying the expression of PRL-induced parental feeding behavior in non-breeding ring doves. Because elevated PRL levels are temporally associated with parental activity during the breeding cycle, these results also implicate the POA in the spontaneous display of parental feeding activity that occurs naturally at the time of hatching.

Animals↗

Serotonergic neurones in the dorsal raphe nucleus that project into the medial preoptic area contain oestrogen receptor beta.

Serotonin is involved in female sexual behaviour in which the medial preoptic area (MPA) has a pivotal role. The present study used immunohistochemistry, in situ hybridization and retrograde transport analysis to investigate whether serotonin neurones in the dorsal raphe nucleus (DRN) of females projecting into the MPA contained oestrogen receptor alpha or beta. The projection of serotonin neurones from the DRN to the MPA was confirmed using the microinjection of Fluoro-Gold (FG), a fluorescent retrograde tracer, into the MPA of ovariectomized (OVX-group) and OVX-rats treated with oestradiol benzoate (E2-group). A number of serotonin neurones in the DRN were labelled with FG, indicating that these serotonin neurones in DRN project their terminals into the MPA. FG-labelled serotonin neurones expressed ERbeta mRNA in the DRN, and the number of the serotonin neurones containing ERbeta mRNA between the OVX-group and the E2-treated group was not significantly different. Serotonin neurones in the DRN did not express ERalpha-immunoreactivity. Since previous findings showed that the density of serotonin-immunoreactive fibres and the concentration of serotonin within the MPA was significantly lower in the E2-group than the OVX-group, our present observations suggested that the regulatory effects of E2 on the serotonergic neurone system in the MPA may be via ERbeta within the serotonin-containing cells in the DRN of female rats.

Animals↗

Effects of prostaglandin E2 on the electrical properties of thermally classified neurons in the ventromedial preoptic area of the rat hypothalamus.

BACKGROUND: Physiological and morphological evidence suggests that activation of the ventromedial preoptic area of the hypothalamus (VMPO) is an essential component of an intravenous LPS-dependent fever. In response to the endogenous pyrogen prostaglandin E2 (PGE2), the majority of temperature insensitive neurons in the VMPO show an increase in firing rate, while warm sensitive neurons are inhibited. We have hypothesized that these PGE2 dependent effects on firing rate are due to changes in the inherent electrical properties of VMPO neurons, which are regulated by the activity of specific ionic currents. RESULTS: To characterize the electrical properties of VMPO neurons, whole-cell recordings were made in tissue slices from male Sprague-Dawley rats. Our results indicate that PGE2 dependent firing rate responses were not the result of changes in resting membrane potential, action potential amplitude and duration, or local synaptic input. However, PGE2 reduced the input resistance of all VMPO neurons, while increasing the excitability of temperature insensitive neurons and decreasing the excitability of warm sensitive neurons. In addition, the majority of temperature insensitive neurons responded to PGE2 with an increase in the rate of rise of the depolarizing prepotential that precedes each action potential. This response to PGE2 was reversed for warm sensitive neurons, in which the prepotential rate of rise decreased. CONCLUSION: We would therefore suggest that PGE2 is having an effect on the ionic currents that regulate firing rate by controlling how fast membrane potential rises to threshold during the prepotential phase of the action potential.

Action Potentials↗

Extracellular dopamine in the medial preoptic area: implications for sexual motivation and hormonal control of copulation.

Dopamine (DA) activity in the medial preoptic area (MPOA) contributes to the control of male rat sexual behavior. We tested (1) whether extracellular DA increases during precopulatory exposure to an estrous female and during copulation, (2) whether exposure to another male increases extracellular DA, (3) whether motor activity during copulation accounts for increased DA levels, and (4) whether concurrent or recent testosterone influences DA levels or copulation in castrates. Extracellular DA and its metabolites in male rats' MPOA were measured using microdialysis. DA level increased during precopulatory exposure to the female in all animals that subsequently copulated; this included all intact animals, all testosterone-treated castrates, and 9 of 14 1-week castrates treated with oil vehicle. DA levels did not increase in any animal that subsequently failed to copulate, including the remaining 1-week, and all 2-week, vehicle-treated castrates. When the barrier was removed and the animals were allowed to copulate, levels of DA and its metabolites continued to rise in intact males and in castrates that copulated. The DA response to the estrous female could not be attributed to nonsexual social stimuli, since exposure to another male was ineffective. The DA response to copulation could not be attributed primarily to motor activity, since animals running voluntarily in a running wheel did not show significantly increased DA. These and previous data suggest that DA released in the MPOA in response to an estrous female may contribute to sexual motivation and copulatory proficiency. Testosterone may promote copulation in part through permissive actions on dopamine release.

Animals↗

Damage of the medial preoptic area impairs peripheral pilocarpine-induced salivary secretion.

The existence of neural connections between the medial preoptic area (MPOA) and the salivary glands and the increase in salivation by thermal or electrical stimulation of the MPOA have suggested an important role of MPOA in the control of salivary gland function. Although direct cholinergic activation of the salivary glands induces salivation, recent studies have suggested that salivation produced by i.p. pilocarpine may also depend on the activation of central mechanisms. Therefore, in the present study, we investigated the effects of bilateral electrolytic lesions of the MPOA on the salivation induced by i.p. pilocarpine. Adult male Holtzman rats (n = 11-12/group) with bilateral sham or electrolytic lesions of the MPOA were used. One, five, and fifteen days after the brain surgery, under ketamine anesthesia, the salivation was induced by i.p. pilocarpine (1 mg/kg of body weight), and saliva was collected using pre-weighed small cotton balls inserted into the animal's mouth. Pilocarpine-induced salivation was reduced 1 and 5 days after MPOA lesion (341 +/- 41 and 310 +/- 35 mg/7 min, respectively, vs. sham lesions: 428 +/- 32 and 495 +/- 36 mg/7 min, respectively), but it was fully recovered at the 15th day post-lesion (561 +/- 49 vs. sham lesion: 618 +/- 27 mg/7 min). Lesions of the MPOA did not affect baseline non-stimulated salivary secretion. The results confirm the importance of MPOA in the control of salivation and suggest that its integrity is necessary for the full sialogogue effect of pilocarpine. However, alternative mechanisms probably involving other central nuclei can replace MPOA function in chronically lesioned rats allowing the complete recovery of the effects of pilocarpine.

Animals↗

Neuronal activity in female rat preoptic area associated with sexually motivated behavior.

Single unit activities were recorded from 31 neurons in the preoptic area (POA) of female rats engaging in sexual interactions. Concurrent videotape recordings were used to establish a relationship between neuronal activity and particular behavioral events. In 14 of the 31 neurons, the firing rate changed in association with bouts of sexual activity. The remaining 17 fired with more variability regardless of episodes of sexual interactions. Peri-event histograms identified four types of neurons: type 1 (n=4) increased their firing rate when the female rats initiated proceptive behavior; type 2 (n=4) showed a brief activation when the male mounted; type 3 (n=4) fired in response to intromission, and type 4 (n=2) were inhibited prior to and throughout the display of lordosis reflex. Type 1 neurons fired at significantly higher rates during the solicitatory period, from the initiation of solicitatory locomotion to the male mounts. Their activity was suppressed when the males mounted successfully with intromission. Types 1-3 neurons were recorded from the transitional region between the medial and lateral POAs. Type 4 neurons were located more medially in the medial POA. Systemic injection of pimozide, a dopamine receptor blocker, diminished firing in type 1 neurons and abolished proceptivity. The firing pattern in type 1 neurons appeared to embody the motivational state of the animal with an implication for a consummatory value of penile intromission. Visceral or somatosensory inputs may be responsible for short bursts in types 2 and 3 neurons. Type 4 neurons behaved exactly as if they inhibit the execution of the lordosis reflex. The results showed separate sets of POA neurons each specifically associated with proceptive and receptive components of female rat sexual behavior.

Action Potentials↗

Estrogen receptive neurons in the preoptic area of the rat are postsynaptic targets of a sexually dimorphic enkephalinergic fiber plexus.

The periventricular preoptic area (pePOA) is a sexually dimorphic component of the rat forebrain that contains a sexually dimorphic Met-enkephalin immunoreactive (ENK-ir) fiber plexus. This plexus is especially dense in the female while only scattered ENK-ir fibers are present in the pePOA of the male. Abundant estrogen receptive neurons are located in the pePOA of both the female and male. This experiment was conducted to determine if estrogen receptive neurons in the pePOA are postsynaptic targets of ENK-ir terminals. Double label ultrastructural localization of estrogen receptor (ER)-ir neurons and ENK-ir fibers was performed using the chromogens 3,3',5,5'-tetramethylbenzidine (TMB) and diaminobenzidine tetrahydrochloride (DAB), respectively. TMB-stained ER-ir neurons contained electron dense crystalline spicules located predominantly in their nuclei. Flocculent DAB reaction product was distributed over membraneous structures in ENK-ir fibers and terminals. Numerous ER-ir neurons were present in the pePOA of the male and female. In females, many ENK-ir terminals, both synaptic and non-synaptic, contacted the perikarya of ER-ir neurons. In contrast, many fewer ENK-ir terminals made contact on ER-ir neurons in the male. Thus, these results provide morphological evidence that ENK-ir neurons can regulate ER-ir neurons in the pePOA. Moreover, because expression of the ENK-ir pePOA fiber plexus is estrogen-sensitive in the female, these results suggest strongly that estrogen may regulate these neurons both pre- and postsynaptically. Finally, these results provide additional evidence for the involvement of the sexually dimorphic pePOA ENK-ir fibers plexus in the control of estrogen-mediated function in the female.

Animals↗

Dual effect of electrochemical stimulation of the medial preoptic area on the release of LH: possible neurotransmitter involvement.

Electrochemical and electrical stimulation of the medial preoptic area (MPA) was shown to induce release of LH in rats. Owing to differences in cytoarchitecture and neural afferents between the medial (mMPA) and lateral (lMPA) parts of the MPA, we decided to explore whether this difference in organization would distinctly influence the secretion of gonadotropin. Both parts of the MPA were electrochemically stimulated on the day of proestrus in freely behaving rats bearing chronic implanted electrodes. An anodic direct current of 100 microA was delivered for 40 s at 11.00 h and blood samples were obtained every hour until 17.00 h. Serum LH concentrations in rats stimulated in the medial part of the MPA showed a robust rise 1 h after the stimulus was applied and the values remained high up to the end of the bleeding period. All these animals ovulated. An initial rise in serum LH was also seen in rats stimulated in the lMPA but serum values thereafter returned to basal levels, significantly lower than those in the mMPA-stimulated or in control, nonstimulated rats. Only 2 rats showed full ovulation and the others failed to ovulate or had partial ovulation. Injection of the serotonin antagonist, methysergide, did not affect the response of rats stimulated in either the mMPA or lMPA. The GABA antagonist, bicuculline, had no effect on LH release evoked by lMPA stimulation but blocked the release induced by mMPA stimulation. This later blockade was partially reversed by the administration of the opioid receptor antagonist, naloxone, suggesting the existence of GABA facilitatory influences on LH release via inhibition of opioidergic inputs to the GnRH neurons. On the other hand, naloxone administration had no effect on LH release evoked by stimulation of the mMPA but partially reversed the inhibition resulting from stimulating the lMPA. These data indicate that the mMPA and lMPA have opposite effects on LH secretion and provide evidence for the possible neurotransmitters involved.

Animals↗

Properties and sex-specific differences of GABAA receptors in neurons expressing gamma1 subunit mRNA in the preoptic area of the rat.

Gamma-aminobutyric acid type A (GABAA) receptors expressed within the medial preoptic area (mPOA) are known to play a critical role in regulating sexual and neuroendocrine functions. In the rat brain, high levels of expression of the gamma1 subunit mRNA of the GABAA receptor are restricted to a limited number of regions that mediate sexual behaviors, including the mPOA. The biophysical and pharmacological profiles of native gamma1-containing receptors in neurons are unknown. Here, we have characterized the properties of GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) and currents elicited by fast perfusion of GABA to isolated mPOA neurons of juvenile male and female rats. No significant sex-specific differences were evident in the mean peak amplitude, distribution of event amplitudes, kinetics of current decay, or the frequency of sIPSCs. The profile of modulation of sIPSCs by diazepam, beta-CCM and zolpidem, allosteric modulators that act at the benzodiazepine (BZ) site of the GABAA receptor, support the assertion that mPOA neurons of both sexes express functional gamma1-containing receptors. The ability of zolpidem to modulate both sIPSC amplitude and currents elicited by rapid perfusion of GABA to mPOA neurons differed significantly between the sexes. Zolpidem reversibly induced negative modulation of currents in mPOA neurons isolated from male rats, but had no effect in mPOA neurons from female rats. Concentration-response analysis of responses in neurons acutely isolated from male rats indicated an IC50 of 58 nM with maximal decreases of approximately 50% of control peak current amplitude. In situ hybridization analysis demonstrated that levels of the gamma1 subunit mRNA are significantly higher in mPOA neurons from male than female rats. No significant sex-specific differences were detected in the levels of alpha1, alpha2, or alpha5 mRNAs. These results suggest that native gamma1-containing receptors are expressed in primary neurons of the mPOA and that sex-specific differences in the expression of this subunit may contribute to sexual dimorphism in GABAA receptor modulation by compounds acting at the BZ site.

Animals↗

Plasma LH levels in the long term ovariectomized rat after anterolateral deafferentation of the medial basal hypothalamus and lesions in the medial preoptic area.

This study was designed to investigate the effect of anterolateral hypothalamic deafferentiation (ALHD) and medial preoptic area (MPOA) lesions on plasma LH levels in the long term ovariectomized rat. The deafferentations were carried out with a Halasz-Pupp knife (radius of 1.5 mm and height of 2.0 mm) and the MPOA lesions with a platinum electrode. Sham treated and an intact group served as controls. Blood samples were obtained from the jugular vein under light ether anesthesia before and at 1, 2, 4 and 6 weeks after brain surgery. After the sixth week sample all rats were treated with 50 micrograms of estradiol benzoate (EB) and two days later blood samples were collected during the morning and afternoon. Hypothalamic deafferentation resulted in a more significant (p less than 0.01) drop in plasma LH levels in one half of the group (ALHD-1) than in the other half (p less than 0.05) (ALHD-2) when compared to the controls. Treatment of the controls with EB resulted in a significant (p less than 0.01) depression of LH levels in the morning and an LH surge during the afternoon. EB also resulted in a suppression (p less than 0.01) of LH levels during the morning in all of the ALDH rats; however, only the ALHD-1 group had an LH surge during the afternoon following EB. Plasma LH levels in the ALHD-2 remained suppressed during the afternoon after EB treatment. Lesions in the MPOA had no effect on plasma LH levels at 1 to 6 weeks when compared to controls. Treatment of the MPOA lesion group with EB resulted in a significant (p less than 0.01) drop in plasma LH levels during the morning as well as the afternoon. These data suggest that the fibers that are critical for the control of tonic and phasic LH secretion enter the medial basal hypothalamus laterally and that the deafferentations carried out here were selective in interrupting fibers involved with tonic LH secretion in some rats and those involved with the phasic secretion in others. These data also suggest that the MOPA components involved with tonic LH secretion are separate from those controlling phasic LH secretion.

Afferent Pathways↗

Expression of prolactin receptor mRNA is increased in the preoptic area of lactating rats.

This study investigated expression of prolactin receptor (PRL-R) mRNA in the preoptic area in midlactating rats compared with diestrous rats. Tissues from specific nuclei were micropunched from 300-microm thick rat brain sections with 300- or 500-microm diameter needles. After total RNA was extracted, the two forms of PRL-R mRNA were evaluated by reverse transcriptase polymerase chain reaction and Southern hybridization. The results showed that levels of long-form PRL-R mRNA in the ventrolateral preoptic nucleus and lateroanterior nucleus in lactating rats were significantly higher (p < 0.05) than in diestrous rats. The ventromedial and medial preoptic nuclei in lactating rats also expressed moderately high levels of long-form mRNA when compared with (p = 0.0547) diestrous rats. The ventromedial and ventrolateral preoptic nuclei, and ventrolateral hypothalamic nucleus in lactating rats expressed significantly higher levels of short-form mRNA than in diestrous rats. The increased expression of both forms of PRL-R mRNA helps explain numerous effects of PRL on brain functions during lactation.

Animals↗

Specific binding of [3H]resiniferatoxin by human and rat preoptic area, locus ceruleus, medial hypothalamus, reticular formation and ventral thalamus membrane preparations.

Specific [3H]resiniferatoxin (RTX) binding detects the vanilloid (capsaicin) receptors and provides a biochemical means for exploring their pharmacology. In the present study we demonstrate specific vanilloid (RTX) binding sites in various brain areas not known to be innervated by primary afferent neurons. Specific high-affinity binding of [3H]RTX could be detected in membrane preparations of the posterior ("hypothalamic") and anterior ("septal") parts of the preoptic area, locus ceruleus, medial hypothalamus, brainstem reticular formation and ventral thalamic nuclei from naive rats. The determined levels of binding at 4 nM [3H]RTX were 23.0 +/- 4.5, 7.1 +/- 1.6, 29.9 +/- 2.3, 23.5 +/- 2.4, 9.9 +/- 2.2 and 8.1 +/- 1.9 fmol/mg, respectively; unfortunately, the high levels of non-specific binding (higher than 80%) in the present experiments made it impossible for us to characterize fully the binding properties of the receptors. However, no detectable specific [3H]RTX binding was present in membranes of brain nuclei from rats pretreated with 300 mg/kg capsaicin, a treatment which causes loss of response to capsaicin. Significant specific [3H]RTX binding was also absent in membrane preparations of the midbrain central gray matter, somatosensory cortex and cerebellum either from naive or capsaicin treated rats. In human brain specific [3H]RTX binding measured at 4 nM [3H]RTX showed a pattern of distribution similar to that in the rat brain. The corresponding levels of specific [3H]RTX binding in the preoptic area, locus ceruleus, medial hypothalamus, reticular formation and ventral thalamus were 44.9 +/- 2.4, 50.6 +/- 3.0, 36.1 +/- 2.9, 9.4 +/- 2.8 and 8.4 +/- 2.4 fmol/mg, respectively. Our findings corroborate previous biological evidence that vanilloid receptors are present in brain as well as in sensory afferent neurons.

Animals↗