Speculations concerning the physiological significance of central oxytocin in maternal behavior.
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Animals↗
Biomedical subjects
M M McCarthy
Publications and source records attributed to M M McCarthy.
Ovarian steroid modulation of [3H]muscimol binding in the spinal cord of the rat.
[3H]Muscimol binding was measured in the lumbar spinal cord of female rats by in vitro quantitative autoradiography. Ovariectomized rats were treated subcutaneously with either oil, estradiol benzoate (EB) or EB plus progesterone (P) in a regime known to reliably induce sexual receptivity. The level of [3H]muscimol binding was highest in laminae I-III and in the region around the central canal. Binding was lower in laminae IV-VI and was frequently undetectable in the ventral horn. There was a significant increase in the level of binding in laminae I-III after EB treatment. There was also a significant increase after treatment with EB+P in comparison to both the ovariectomized and EB-treated groups in this same region of the spinal cord.
Animals↗
Excitatory amino acid modulation of lordosis in the rat.
Microinfusion of the excitatory amino acid agonist N-methyl-D-aspartate (NMDA) into the mediobasal hypothalamus (MBH) significantly reduced lordosis in estrogen plus progesterone-treated female rats at 10 min post-infusion with recovery to pretest values by 30 min (P less than .05; Wilcoxon). Microinfusion of the specific NMDA antagonist D,L2-amino-5-phosphonopentoic acid (AP-5) into the same sites was without effect on lordosis responding of fully receptive females. There was also a significant increase in the number of females vocalizing to mounts by males after infusion of NMDA but not after infusion of AP-5 into the MBH. When NMDA was infused into the preoptic area (POA) there was no effect on lordosis responding of full receptive females, but AP-5 infusion resulted in a significant inhibition of lordosis at 10 min post-infusion. There was no difference between groups in percentage of females vocalizing after drug infusion into the POA. These results suggest that increased excitatory amino acid activity in the MBH and decreased excitatory amino acid activity in the POA inhibits lordosis behavior.
2-Amino-5-phosphonovalerate↗
Midbrain central gray GABAA receptor activation enhances, and blockade reduces, sexual behavior in the female rat.
The inhibitory neurotransmitter, GABA, has been implicated in the control of lordosis behavior. Previous studies indicate that modulation of GABAA transmission can have dual effects on lordosis, being facilitative in the ventromedial hypothalamus and inhibitory in the preoptic area. The midbrain central gray (MCG) is also known to be an important neural site for regulating lordosis as well as defensive and escape behaviors, and plays an integral role in the control of nociception. Because of the multitude of behaviors regulated at the level of the MCG, we utilized a two-chamber testing apparatus that allowed simultaneous measurement of the females' proceptive (hopping and darting), receptive and rejection behaviors, as well as an index of nociception and general motor activity. We found that microinfusion of the GABAA antagonist, bicuculline, into the MCG of steroid-primed female rats resulted in a significant decrease in lordosis and proceptive behaviors at 5 min post-infusion. There was full recovery to pretest levels by 60 min. Furthermore, microinfusion of the GABAA agonist, muscimol, to estrogen-treated females that displayed low levels of receptivity and high levels of rejection behavior during a pretest, resulted in a significant increase in lordosis responding and a decrease in rejection behaviors. Neither drug significantly affected time spent in the vicinity of the male, motor activity or vocalizations. It is concluded that the decrease in lordosis resulting from blockade of GABA transmission is not solely due to the induction of antagonistic behaviors since there was no increase in rejections after bicuculline administration. The current findings are consistent with the interpretation that GABA facilitates lordosis in the MCG via disinhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
GABAergic control of receptivity in the female rat.
GABAergic neurotransmission has been implicated in the control of the steroid-dependent behavior, lordosis. GABA has dual effects on lordosis: it facilitates lordosis through actions in the medial hypothalamus (mHYP) and it inhibits lordosis through actions in the preoptic area (POA). In the present study, gonadally intact and ovariectomized female rats were behaviorally tested with a sexually active male. Brains were removed from sexually receptive female either 1 or 24 h after behavioral testing. There was a significant difference in endogenous GABA concentration in HYP and POA between receptive, postreceptive and ovariectomized nonreceptive females. Specifically, GABA levels in postreceptive females were higher in the HYP (20%) and lower in the POA (21%) in comparison to receptive females (p less than 0.05). There was also a significant change in binding parameters of 3H-muscimol in the HYP and POA of receptive females as compared to 24 h postreceptive and ovariectomized rats. Attempts to modulate 3H-GABA release from hypothalamic tissue slices by estrogen or progesterone in ovariectomized rats yielded no effect on this parameter.
Animals↗
Increased GABAergic transmission in medial hypothalamus facilitates lordosis but has the opposite effect in preoptic area.
The role of gamma-aminobutyric acid (GABA) in mediation of lordosis in the rat has been unclear. We report here that GABA plays a dual role in the mediation of lordosis and has differential effects in the medial hypothalamus (MH) and preoptic area/anterior hypothalamus continuum (POA-AH). Bilateral infusion of the GABAA antagonist bicuculline into the MH of cannulated females primed with estradiol benzoate and progesterone (EB + P) resulted in a marked and transient inhibition of ongoing lordosis. A similar pattern of inhibition was seen in females treated with EB only. In contrast, infusion of the same dose of bicuculline into the POA-AH of sexually receptive females had no effect on lordosis whereas infusion of the GABAA agonist muscimol into this site resulted in a short-term inhibition of lordosis. Furthermore, when females were treated with subthreshold doses of EB + P to induce a low level of lordosis responding, infusion of muscimol into the MH resulted in a significant enhancement of lordosis; infusion of bicuculline into the POA-AH also enhanced lordosis responding as compared to saline-infused controls. These data indicate that increased GABAergic neurotransmission in the MH facilitates lordosis whereas increased GABAergic activity in the POA-AH inhibits this behavior.
Animals↗
Oxytocin inhibits infanticide in female house mice (Mus domesticus).
Between 60 and 90% of female house mice spontaneously kill unrelated young. A previous report indicated that subcutaneous administration of oxytocin significantly reduced the frequency of infanticide by virgin and pregnant females. However, in this study a distinction could not be made between an action of oxytocin on the CNS versus a secondary effect such as an enhanced release of prolactin by oxytocin. In the current experiment, oxytocin administered intracerebroventricularly was equally as effective at inhibiting infanticide as sc oxytocin. There was no difference in the effectiveness of oxytocin between groups of infanticidal females that were gonadally intact, ovariectomized, or estrogen treated. Pretreatment of infanticidal females with the prolactin inhibitors, bromocriptine and cysteamine, was also without effect on the ability of oxytocin to inhibit infanticide. Last, prolactin-inhibiting drugs had no significant effect on spontaneous parenting behavior by female mice. These data suggest that oxytocin acts directly on the CNS to alter behavior toward pups and that prolactin may not play a role in the maternal behavior of the house mouse.
Animals↗
Modulation by estrogen and progesterone of the effect of muscimol on nociception in the spinal cord.
The GABAA agonist, muscimol, administered intrathecally (IT) to the spinal cord at a dose (1 microgram) that was subthreshold for affecting pain thresholds (vocalization-threshold-to-tail-shock: VTTS, and tail-flick latency: TFL) in ovariectomized, hormonally untreated rats, showed a significant increase in VTTS up to 30 min postinjection in intact females only in proestrus or estrus. This treatment produced no significant effect on TFL at any stage of the estrous cycle. IT muscimol produced a significant increase in VTTS (but not TFL) in ovariectomized rats primed with estradiol benzoate (EB) for 2 days and tested 40 hr after the second injection but had no effect in females primed with a single EB injection and tested 15 min later. By contrast, ovariectomized females primed with progesterone (P) for 15 min exhibited a significant increase in pain thresholds after IT muscimol in both the VTTS and TFL tests. When EB-primed females (2 days) received P 4 hr prior to muscimol there was no analgesia produced by IT muscimol, in contrast to EB-primed females receiving P 15 min prior to IT muscimol in which there was significant analgesia. These results suggest a mechanism for antagonistic effects of estrogen and progesterone.
Animals↗
Short-term early exposure to pups alters infanticide in adulthood in male but not in female wild house mice (Mus domesticus).
Male and female wild house mice (Mus domesticus) were allowed to remain in the cage of their parents until 30-35 days of age. When a second litter was delivered, the first litter was exposed to the younger pups for 2-10 days. In adulthood the male and female mice that had been exposed to pups as juveniles and an additional group that had cohabitated with their parents for the same length of time but were not exposed to pups were tested for infanticidal behavior. The frequency of infanticide by the adult female mice was not significantly different (55% vs. 70%, respectively). In contrast, the adult males that were exposed to pups as juveniles were significantly less likely to kill young in adulthood when compared with males that were not similarly exposed (35% vs. 80%, respectively). These data further demonstrate the strong influence of experience on the expression of infanticide by male mice and its relative unimportance to the expression of female infanticide.
Animals↗
Barbiturate-induced analgesia: permissive role of a GABAA agonist.
Three doses (0.025, 0.25 and 2.5 mg) of the short-acting barbiturate, pentothal, were injected intrathecally at the lumbar level of the spinal cord of female rats and did not produce analgesia in either the tail-flick latency to radiant heat (TFL) or vocalization-threshold-to-tail-shock (VTTS) tests. However, when the high dose of pentothal (2.5 mg) was given in combination with a nonanalgesia producing dose of the GABAA agonist muscimol (1 microgram), a significant and prolonged analgesia was produced in both the VTTS and TFL tests, lasting up to one hour postinjection. Intrathecal injection of the intermediate dose of pentothal (0.25 mg) in combination with 1 microgram muscimol also produced significant analgesia in the TFL but not the VTTS test. We suggest that barbiturates may act on spinal nociceptive pathways to reduce pain thresholds only when sufficient GABAergic activity is present.
Analgesics↗
Conscious guinea-pig aerosol model for evaluation of peptide leukotriene antagonists.
A new conscious animal model for evaluating leukotriene antagonists is described. The model consists of monitoring the change in the respiratory pattern induced by aerosol administration of various airway constrictors in six guinea pigs secured in a plexiglass chamber by a neck yoke. The animals are pretreated with indomethacin (10 mg/kg, i.p.) and propranolol (5 mg/kg, i.p.) 30 min prior to the challenge. After a 30-min stabilization period, the animals are challenged by various agonists delivered via a Monaghan ultrasonic nebulizer at a flow rate of 2.0 L/min for 5 min. The end point is defined as the onset of slow, labored abdominal breathing (dyspnea) measured in seconds. Peptide leukotrienes (LTs) (30 nM-60 microM) produced concentration-related decreases in time to dyspnea with a rank order of potency of LTD4 greater than LTC4 greater than LTE4. LTD4 was 1,000-fold more potent than histamine or carbachol. Pretreatment of the animals with either FPL55712 or LY171883 delayed the time to reach dyspnea induced by LTD4. In contrast, pyrilamine, cyproheptadine, and phenoxybenzamine failed to alter LTD4-induced dyspnea. The results indicate that this model is useful in assessing the efficacy of LT receptor antagonists in vivo.
Administration, Inhalation↗
Infanticide by virgin CF-1 and wild male house mice (Mus musculus): effects of age, prolonged isolation, and testing procedure.
The frequency of infanticide by juvenile, young-adult, and adult male house mice (Mus musculus) was compared in CF-1 albino mice and the F1-F4 male offspring of wild mice trapped in Missouri. When tested in their home cages for their behavior toward a single 2-day-old pup after being individually housed for 5 days, juvenile CF-1 and wild males were equally likely to exhibit infanticide (about 35%). But, adult wild males were significantly more likely to exhibit infanticide (about 90%) than were adult CF-1 males (about 45%). We propose that differences in exposure to testosterone during fetal life may contribute to the difference in the incidence of infanticide between CF-1 and wild males. Prolonged isolation (45 days) significantly reduced the proportion of wild male mice that exhibited infanticide when the males were tested in their home cages, but not when the males were tested by being placed into the cage of lactating females and their 2-day-old young. Virtually all adult wild males exhibited infanticide when they were tested in their home cages (with either a 2-day-old or 7-day-old pup) or when they were placed into the cages of lactating wild female mice and their 2-day-old young. But, when adult wild males were placed with lactating wild females on Day 7 postpartum, the females attacked the males and most males were prevented from exhibiting infanticide.
Aging↗
Inhibition of infanticide after mating by wild male house mice.
The effect of mating on the behavior of male house mice (Mus musculus) toward young has been examined in numerous domestic stocks of mice, and the somewhat contradictory results led us to examine the effects of mating on the behavior of wild male mice toward young. The wild mice were the F1-F4 offspring of mice trapped in Missouri. Virtually all wild males exhibit infanticide prior to mating, but virrually all wild males were inhibited from exhibiting infanticide 3 weeks after mating whether they were placed into the cage of their former mate and her litter or into the cage of an unfamiliar female and her litter, similar to the effect of mating on the behavior of CF-1 male mice toward young. In contrast, wild males that had exhibited infanticide prior to mating were inhibited from exhibiting infanticide 3 weeks after mating when placed with their former mates and their 2-day-old young but not when placed with unfamiliar females and their 2-day-old young. When wild males were tested for their behavior toward young using the procedure of placing a single pup into each male's home cage, mating did not result in an inhibition of infanticide (about 90% of the males exhibited infanticide). Cohabitation with a female without mating also did not influence the behavior of wild males toward young. Wild males that exhibited infanticide when placed with a lactating female produced their own young more rapidly than did noninfanticidal males, thus providing further support for the hypothesis that under some conditions, infanticide can be an adaptive trait.(ABSTRACT TRUNCATED AT 250 WORDS)
Adaptation, Biological↗
Infanticide and parental behavior in wild female house mice: effects of ovariectomy, adrenalectomy and administration of oxytocin and prostaglandin F2 alpha.
We have previously observed that about 60% of virgin, wild female house mice (Mus musculus), that were the offspring of wild mice trapped in Missouri, exhibited infanticide when a single 2-day-old pup was placed into each female's home cage. But, by the end of pregnancy, there was a significant increase (to 90%) in the proportion of wild female mice that exhibited infanticide. At parturition, infanticide was inhibited and parental behavior was induced in all females. In the present study we examined the influence of ovarian and adrenal hormones, as well as two hormones associated with pregnancy and parturition: oxytocin and prostaglandin F2 alpha (PGF), in regulating infanticide and parental behavior in wild female house mice. The presence or absence of gonadal and adrenal hormones did not influence the frequency of infanticidal behavior in adult female mice. Subcutaneous injections of either oxytocin or PGF inhibited infanticide in previously infanticidal pregnant females 1 hr after injection, but only oxytocin served to also facilitate parental behavior (most PGF-treated females left the pup untouched). Oxytocin, but not PGF, was effective in inhibiting infanticide in previously infanticidal virgin females. These findings suggest that, by themselves, ovarian and adrenal hormones do not mediate the exhibition of infanticide by wild female mice, but the lack of response to PGF in virgin females suggests that endocrine changes during pregnancy (possibly changes in steroids) may modulate the inhibitory effects of PGF on infanticide.
Adrenal Cortex Hormones↗
The influence of reproductive state on infanticide by wild female house mice (Mus musculus).
The majority of female mice (Mus musculus) from laboratory stocks are spontaneously parental. In contrast, the majority of adult wild female house mice exhibit infanticide (the killing of preweanling young), but the frequency with which infanticide is observed varies as a function of age and reproductive state. Prepubertal females were less likely to exhibit infanticide (39%) than were adult virgin females (61%). The frequency of infanticide increased during pregnancy, with over 90% of females exhibiting infanticide just before parturition. But, after parturition, previously infanticidal females cared for their own litters. When lactating female mice were tested after two days of separation from their own nursing young for their behavior toward a novel newborn pup on either the tenth or twenty-fifth day after parturition, the proportion of the females that exhibited infanticide was not significantly different from that of adult virgin females (about 60%). After only two hours of separation from their own nursing young on the tenth day after parturition, however, all females continued to exhibit parental behavior toward a novel pup.
Aggression↗
Childhood asthma hospitalization rates in Spokane County, Washington: impact of volcanic ash air pollution.
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Adolescent↗