Inactivation of the medial preoptic area/anterior hypothalamus by lidocaine reduces male sexual behavior and sexual incentive motivation in male rats

Permanent bilateral lesions of the medial preoptic area anterior hypothalamus (MPOA/AH) produce a drastic inhibition of male sexual behavior in all species studied to date. The present experiment was designed to evaluate if temporal inactivation of the MPOA/AH by infusions of lidocaine also inhibits sexual behavior in male rats. This would allow us to rule out the possibility that the behavioral effects observed after damage of the MPOA/AH could be associated with plastic changes induced by the lesion in other brain regions. We also evaluated sexual incentive motivation in males after the infusion of lidocaine in a test in which copulation is not possible but where males maintain approach behavior to the estrous females despite repeated testing. The percentage of animals displaying mounts, intromissions and ejaculation was significantly reduced while mount and intromission latency were prolonged after infusion of lidocaine. No changes were observed in sexual behavior after infusion of lidocaine in animals with cannulae outside the MPOA/AH suggesting that the inhibitory effects are specific to this brain region. Sexual incentive motivation was also affected by administration of lidocaine. Males consistently showed a clear preference for the sexually receptive female except when infused with lidocaine. After the infusion of the compound a significant reduction in the time spent in the incentive zone of the stimulus female was observed. These results support the hypothesis that neurons of the MPOA/AH are involved in the control of male sexual motivation.     

A second look at the barriers of the medial basal hypothalamus

The cell bodies of hypothalamic secretory neurons are localized in areas protected by the blood-brain barrier (BBB), whereas their axon terminals are localized in the median eminence, which lacks a BBB. This implies a complex barrier system, allowing neurons of the central nervous system to secrete into the blood stream without making the BBB leaky. In the present study, three experimental protocols were applied to clarify certain relevant aspects of the barriers operating in the medial basal hypothalamus of the rat. We established that the milieu of the arcuate nucleus is exposed to both the ventricular and the subarachnoidal cerebrospinal fluid (CSF).The median eminence milieu, the perivascular space of the portal vessels, and the subarachnoid space appear to be in open communication; also, beta2-tanycytes establish an efficient barrier between the median eminence milieu and the ventricular CSF. Similarly, beta1-tanycytes establish a lateral barrier, separating the intercellular space of the median eminence from that of the arcuate nucleus. We also found that the glucose transporter I (GLUT I), a BBB marker, is localized throughout the whole plasma membrane of beta1-tanycytes, but is missing from beta2-tanycytes. Expression of GLUT I by tanycytes progressively develops during the first postnatal weeks; while the degree of damage of the arcuate nucleus by administration of monosodium glutamate, at different postnatal intervals, parallels that of the GLUT I immunoreactivity of beta1-tanycytes. An explanation is offered for the selective destruction of the arcuate neurons by the parenteral administration of monosodium glutamate to infant rats.     

In vivo release of neurotransmitters in the medial basal hypothalamus of the monkey

Summary In vivo release rates of norepinephrine (NE), epinephrine (E), dopamine (DA), gammaaminobutyric acid (GABA), glutamate (GLU) and beta-endorphin (E) in the medial basal hypothalamus (MBH) of unanaesthetized female macaca fascicularis monkey, and the effects thereon of estrogen (E2) treatment, have been estimated using pushpull perfusion methodology. DA, NE, E, GABA, GLU and E were all detectable in 30 min perfusate fractions. No direct correlation between their release rates and those of LH and PRL could be observed. E2 induced an initial decrease, then an increase, in LH and PRL secretion, and concomitant changes in the release patterns of DA, NE, E. GABA and GLU were apparent. This study demonstrates that in vivo push-pull perfusion methodology may be applied to the unanaesthetized monkey, and when combined with venous catheterization for serial blood sampling may prove to be a powerful tool in the investigation of the central molecular events governing neuroendocrine functions.     

Responses of cat preoptic neurons to stimulation of the medial frontal cortex and the medial basal hypothalamus

Summary Responses of single preoptic neurons to electrical stimulation of the medial frontal cortex, the mediobasal hypothalamus (MBH) and the medial forebrain bundle (MFB) were recorded in anaesthetised cats. Single pulse stimulation of the medial frontal cortex orthodromically drove 96 otherwise quiescent preoptic neurons, which were found more frequently in the dorsal preoptic region, inhibited 53% of the spontaneously active preoptic neurons and excited 16%. Testing of cortically influenced preoptic neurons with MBH or MFB stimulation resulted in antidromic invasion of 6% (MBH) and 9% (MFB). Convergence of orthodromic inputs from medial frontal cortex and MBH was detected in 78% of spontaneously active preoptic neurons, and three-way convergence including input from MFB was noted in 17% of neurons tested with all stimulators. Some cortex-responsive neurons were found to also respond to vaginal or anal probing, paw squeezing and haemorrhage. The role of this input to the preoptic region from medial frontal cortex remains to be elucidated, but may include neuroendocrine, behavioural and homeostatic functions.     

The effect of prolactin on dopamine release from rat striatum and medial basal hypothalamus

Electrical stimulation of supervised rat striatal slices or medial basal hypothalamus evokes a calcium-dependent release of dopamine; the release is blocked by tetrodotoxin. Prolactin (0.5–5 μg/ml) enhanced the evoked release of dopamine from both these tissues.It is well known that dopamine will inhibit the release and synthesis of prolactin in the pituitary. Our results suggest a possible presynaptic effect of prolactin on dopamine release.     

The connections of the medial preoptic region and maternal behavior in the rat

Female rats which are hysterectomized and ovariectomized on Day 16 of pregnancy and injected with estrogen show a short latency to onset of maternal behavior when presented with test pups 48 hrs later. In the present experiment, female rats were treated similarly except that on Day 16 of pregnancy they received knife cuts which severed either the lateral, anterior, dorsal, or posterior connections of the medial preoptic area (MPOA), or sham knife cuts. Severing the lateral connections of the MPOA severely disrupted materal behavior, while severing the dorsal or posterior connections of the MPOA produced either minor deficits or no deficits. Severing the anterior connections of the MPOA did produce large deficits in maternal behavior, but this was associated with hypoactivity and loss of body weight. Therefore, the maternal behavior deficits observed in the anterior cut group may have been a secondary effect of the knife cut. The results emphasize the importance of the lateral connections of the MPOA for maternal behavior.     

Neuronal organization of the thermosensory region of the anterior hypothalamus

Changes in extracellular unit activity of 236 neurons of the medial preoptic and septal regions to local temperature stimulation were studied in acute experiments on rabbits anesthetized with urethane and chloralose. Of this total number of neurons 27% were highly sensitive to changes in brain temperature (15% to heat, 12% to cold). Altogether 6% of neurons gave an on-response and 5% a prolonged after-effect to temperature stimulation. The possible role of these neurons in the regulation of temperature homeostasis is discussed.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 62, No. 2, pp. 175–181, February, 1976.     

Cytokine modulation of defensive rage behavior in the cat: role of GABAA and interleukin-2 receptors in the medial hypothalamus

Defensive rage behavior is a form of aggressive behavior occurring in nature in response to a threatening stimulus. It is also elicited by stimulation of the medial hypothalamus and midbrain periaqueductal gray (PAG) and mediated through specific neurotransmitter-receptor mechanisms within these regions. Since interleukin (IL)-2 modulates the release of neurotransmitters linked to aggression and rage, we sought to determine whether IL-2 microinjected into the medial hypothalamus would modulate defensive rage. Microinjections of relatively low doses of IL-2 into the medial hypothalamus significantly suppressed defensive rage elicited from the PAG in a dose-dependent manner and in the absence of signs of sickness behavior. Pre-treatment with an antibody directed against IL-2Ralpha or a GABA(A) receptor antagonist blocked IL-2's suppressive effects upon defensive rage. Since the suppression of defensive rage is also mediated by 5-HT(1) receptors in the medial hypothalamus, a 5-HT(1) antagonist was microinjected into this region as a pretreatment for IL-2; however, it did not block IL-2's suppressive effects. Immunocytochemical data provided anatomical support for these findings by revealing extensive labeling of IL-2Ralpha on neurons in the medial hypothalamus. IL-2 microinjected into the medial hypothalamus did not modulate predatory attack elicited from the lateral hypothalamus. In summary, we provide evidence for a novel role for IL-2 in the medial hypothalamus as a potent suppressor of defensive rage behavior. These effects are mediated through an IL-2-GABA(A) receptor mechanism.     

Influence of cholinergic agents on dopamine release from medial basal hypothalamus.

The ability of acetylcholine to influence the stimulation-induced release of [3H]dopamine in medial basal hypothalamus was evaluated. A muscarinic facilitation of electrical field-stimulated but not potassium-stimulated release was observed. These data suggest a muscarinic enhancement of dopamine release perhaps via an action at the level of the cell body. These data suggest that observed effects of cholinergic agents on prolactin release may be mediated in part through such a cholinergic-dopaminergic interaction.     

Pituitary lactotroph sedimentation profiles and in vitro secretory activity after ablation of the medial basal hypothalamus

Pituitary cells from adult male rats subjected to chronic (6 and 10 weeks) medial hypothalamic ablation (MHA) were analyzed by unit gravity sedimentation to assess distribution of size and density of lactotrophs, and for subsequent in vitro prolactin (PRL) release in primary culture. Tinctorial staining (Herlant's tetrachrome) showed that initial preparations of cells from MHA rats were small and relatively undifferentiated. MHA cells did not sediment as far into the gradient as did cells from intact control pituitaries. Intracellular PRL content was lower in all gradient fractions of MHA cells. At 6 weeks after surgery, peak recovery of PRL was also in the upper portions of the gradient. In the 10-weeks group, however, peak PRL recovery from MHA cells was in a population that sedimented further, but more restrictedly, in comparison with control cells. At both postsurgical intervals, the majority of tinctorially or immunocytochemically identified lactotrophs from lesioned rats were lower in the gradient, indicating enlarged and denser cells. Relative numbers of lactotrophs (per pituitary) were increased 10 weeks after MHA. In vitro PRL release, over a maximum of 21 days culture, was comparable for cells from MHA rats and intact controls, according to daily per cell secretion rates and "production index" (hormone released/initial hormone content). By comparison, luteinizing hormone (LH) release was suppressed in culture compared to intact controls, and LH was recovered from gradient fractions of smaller cells. The results indicate that chronic removal of hypothalamic influence results in gradual prolactin cell hypertrophy and decreased hormone retention and in relative increase in numbers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunocytochemical localization of luteinizing hormone-releasing hormone in neurons in the medial basal hypothalamus of the female rat

Summary Luteinizing hormone-releasing hormone (LHRH)-neurons were localized with a LHRH antiserum (WP-1) in the medial basal hypothalamus (MBH) of the female rat using the sagittal hypothalamic slice preparation in combination with the peroxidase-antiperoxidase immunocytochemical technique of Sternberger (1979). Numerous darklystained perikarya were visualized in the cell-poor zone, lateral arcuate nucleus and the median eminence. The processes of these neurons contributed to the intensely-stained fiber bundle above the tubero-infundibular sulcus. The fibers in this tract run in a rostrocaudal plane in the lateral external zone of the median eminence. Also, numerous fibers course into the internal zone of the median eminence, perpendicular to the rostrocaudal plane. Several LHRH-immunoreactive perikarya also were identified in the periventricular area caudal to the optic chiasm (retrochiasmatic area). The LHRH neurons were small (10 m) bipolar neurons with fibers (dendrites) exiting from either pole which showed very little branching. It appears that the sagittal slice in combination with the appropriate fixation procedure and LHRH antiserum enabled us to demonstrate the presence of LHRH-immunoreactive perikarya in the MBH of the female rat.Supported by Health Research Services Foundation Grant W-22 and NIH Grant NS16419     

Stimulation of the hypothalamus and ovulation in the guinea-pig

1. Various methods of stimulating the hypothalamus were applied to the guinea-pig with the aim of inducing ovulation.2. Electrochemical stimulation of the hypothalamus, or gross stimulation of the brain, was ineffective.3. Electrical stimulation of the medial basal hypothalamus or rostral hypothalamus elicited gonadotrophin release.4. Despite variation of the time and intensity of stimulation, follicular luteinization was more common than the formation of new corpora lutea.5. Electrical stimulation of the medial basal hypothalamus often caused luteinization of follicles. Fewer animals responded to excitation of the rostral hypothalamus, but in those that did, ovulation occurred more frequently.6. The present observations contrast markedly with comparable studies on the rat, where both electrochemical and electrical stimulation of the hypothalamus readily induce ovulation.     

Dopamine, the medial preoptic area, and male sexual behavior

The medial preoptic area (MPOA), at the rostral end of the hypothalamus, is important for the regulation of male sexual behavior. Results showing that male sexual behavior is impaired following MPOA lesions and enhanced with MPOA stimulation support this conclusion. The neurotransmitter dopamine (DA) facilitates male sexual behavior in all studied species, including rodents and humans. Here, we review data indicating that the MPOA is one site where DA may act to regulate male sexual behavior. DA agonists microinjected into the MPOA facilitate sexual behavior, whereas DA antagonists impair copulation, genital reflexes, and sexual motivation. Moreover, microdialysis experiments showed increased release of DA in the MPOA as a result of precopulatory exposure to an estrous female and during copulation. DA may remove tonic inhibition in the MPOA, thereby enhancing sensorimotor integration, and also coordinate autonomic influences on genital reflexes. In addition to sensory stimulation, other factors influence the release of DA in the MPOA, including testosterone, nitric oxide, and glutamate. Here we summarize and interpret these data.     

The role of female movement in the sexual behavior ofDrosophila melanogaster

NormalDrosophila melanogaster males rapidly react to changes in the mobility of mutantshibire ^ts females by performing less courtship when the females are paralyzed and by courting movingshibire ^ts females vigorously. Mutantoptomotor-blind males, which are unable to respond to certain horizontally moving patterns, sustain abnormally short courtship bouts when tested with normal females, almost never perform orientation, one of the courtship behaviors, and require more time to initiate copulation than normal males. These results suggest that males must perceive female movement to perform normal courtship and copulation. Normal females become stationary before copulation occurs. Normal males mate quickly in response to this change in female behavior, while blind males require more time to effect copulation, prolonging the time that the female remains stationary. Mutantsmellblind females, which do not respond to certain odors, continue to move during the time that they are courted by normal or blind males and also require more time to copulate, suggesting that females may stop moving before mating in response to olfactory cues.This research was supported by U.S. Public Health Service Grant GM 21473 to J.C.H., who is also supported by U.S. Public Health Service Research Career Development Award GM00297.     

The role of reinforcement in the sexual behavior of the female rat

In order to clarify the role of reinforcement in the sexual behavior of female rats, females were trained to traverse a runway to achieve contact with incentive males. Females learned to run faster to sexually active males that achieved intromission than to passive males (p<0.05). However, both types of incentive males produced significant learning (p< 0.001). The type of estrus, either natural or hormone-induced, did not affect learning measures. The results were interpreted as requiring that an explanatory model of the female's sexual behavior contain a variable accounting for reinforcement specific to sexual contact as well as for the more general social reinforcement and the well established aversive consequences of mating.     

Vasopressin release from rat medial basal hypothalamus in vitro after adrenalectomy or lesions of the paraventricular nuclei

Rat medial basal hypothalami (MBH) or neurointermediate lobes of the hypophysis (NIL) were superfused in vitro and stimulated electrically. The evoked release of vasopressin from the MBH was enhanced to 700% of controls when the tissue was taken from adrenalectomized rats. By contrast, the evoked release of vasopressin from the NIL was not changed after adrenalectomy. After bilateral lesions of the paraventricular nuclei, the evoked release of vasopressin from the MBH was reduced in subsequent in vitro experiments. The marked changes in vasopressin release occurred in spite of no or only small changes in the total tissue content of vasopressin. These data support the view that vasopressin may be released from the external layer of the median eminence into the hypophysial portal blood after activation of the hypothalamo-pituitary-adrenal axis.     

The anterior basal lobe and control of prey-capture in the cuttlefish (Sepia officinalis)

The predatory behaviour of the cuttlefish comprises several stages: prey-detection, orientation, translation and prey-seizing. In this neuroethological study, lesions to the anterior basal lobe were made by an electrolytic method and the animals were allowed to attack their prey in an unrestricted way so that motor defects, functional recovery and the emergence of new adaptative behavioural strategies could be studied. Lesions to the central region of the anterior basal lobe suppress the orientating behaviour, thus only prey situated in the frontal visual field can be seized. Less extensive lesions in this region are associated with similar defects. Without head orientation, the cuttlefish still rotates with its fins. This rotation, however, is usually underestimated, tentacular ejection thus missing the prey. Dorsal lesions cause an underestimation of tentacular strike often associated with defects in maintaining ocular convergence. These results demonstrate the heterogenous function of the anterior basal lobe and its complex role in the control of predatory behaviour.