Alcohol, allopregnanolone and aggression in mice.

RATIONALE: Aggressive behavior of certain individual animals can be greatly increased when under the influence of low doses of alcohol. One of alcohol's neurochemical actions that may be relevant to alcohol-heightened aggression (AHA) is its positive modulation of the GABA(A) receptor complex. OBJECTIVE: The objective of this study was to investigate whether alcohol interacts with an endogenous modulator of the GABA(A) receptor complex, the neurosteroid allopregnanolone, in stimulating/heightening aggressive behavior. METHODS AND RESULTS: The first experiment was designed to test the hypothesis that neurosteroid modulators of the GABA(A) receptor complex will increase aggression and to compare these effects with alcohol. Male CFW mice were injected with allopregnanolone, alphaxalone (3-30 mg/kg, i.p.), or alcohol (1.0 g/kg, p.o.) 15 min prior to a 5-min confrontation with an intruder. Moderate doses of alcohol and the neurosteroids increased aggression by ca. 50% above baseline; impaired locomotion was seen only at the highest doses. A second experiment compared AHA and ANA (i.e. alcohol-non-heightened aggression) mice by giving allopregnanolone (1-10 mg/kg) with a simultaneous oral injection of alcohol (0.6 or 1.0 g/kg) or water. When administered with water and the 0.6 g/kg dose of alcohol, allopregnanolone increased the aggression of AHA and ANA mice. Administration of the 1.0 g/kg dose of alcohol in ANA mice prevented allopregnanolone-heightened aggression. In AHA mice, addition of allopregnanolone to 1.0 g/kg alcohol dose-dependently reduced alcohol-heightened aggression, suggesting potentiation of alcohol's suppressive effects on aggression. CONCLUSIONS: The neuroactive steroid allopregnanolone appears to play an important role in alcohol-heightened aggression. Moreover, the upward shift of the aggression-heightening effects of alcohol and the downward shift at the maximally effective alcohol dose by allopregnanolone point to a shared mechanism for both positive modulators of the GABA(A) receptor complex.

Fos expression in female hamsters after various stimuli associated with mating.

Detection of the expression of c-fos mRNA or its protein product, Fos, has been used to indicate differences in neuronal response to exogenous stimuli. Factors contributing to differences in Fos expression as a result of various stimuli associated with mating have been extensively studied in the female rat. Less is known about the factors that contribute to Fos expression in female hamsters. Female hamsters differ from female rats in several aspects of sexual behavior; therefore, it seems likely that Fos expression may also differ. The purpose of this study was to determine which factors associated with mating selectively affect Fos expression in the female hamster. Animals were ovariectomized, hormone treated, and then exposed to several behavioral conditions. Fos expression in several brain areas was then assessed via immunocytochemistry (ICC). As has been found by others, mating increases Fos immunoreactivity in a number of brain regions. Specifically, vaginal-cervical stimulation (VCS) was determined to be the salient factor contributing to Fos expression in the preoptic area (POA) and bed nucleus of the stria terminalis (BNST) of ovariectomized hormone primed female hamsters that received a mating interaction.

Protein synthesis in the medial preoptic area is important for the mating-induced decrease in estrus duration in hamsters.

Sexual receptivity in female hamsters potentially lasts for about 16 h. However, vaginal cervical stimulation (VCS) from a male during mating eventually reduces receptivity and can shorten the duration of behavioral estrus. The process by which this change in response to the male takes place is unknown. Recently, detection of the Fos protein has indicated that the medial preoptic area (POA) is one of the brain regions particularly responsive to VCS. Additionally, the POA may have an inhibitory effect on sexual receptivity. To determine if protein synthesis in the POA is required to initiate the VCS-induced decrease in estrus duration, a protein synthesis inhibitor (anisomycin, 0.50 microg) or a control substance (cholesterol) was applied bilaterally to the POA of steroid-primed ovariectomized female hamsters. Females were tested with a sexually active male at five time points following the initial test for sexual receptivity (hour 1, 2, 6, 12, and 24). Half of the females tested were allowed to receive VCS from a male, while half were fitted with vaginal masks to prevent penile intromission. Each group receiving VCS showed a significant decrease in lordosis duration evident between hour 2 and hour 6, except the group which received anisomycin in the POA. In this respect the POA anisomycin group was similar to animals which did not receive VCS. Hamsters with vaginal masks and the anisomycin/POA animals allowed to receive VCS exhibited their first decrease in lordosis duration between hour 6 and hour 12. These results indicate that protein synthesis is important for VCS-induced decrease in estrus duration in the POA.

Alcohol, GABAA-benzodiazepine receptor complex, and aggression.

Neurobiological investigations have become productive since experimental protocols were developed that engender large increases in aggressive behavior after acute alcohol challenges in individual experimental animals. Recent developments extended the heightened aggressive behavior to rats that self-administered alcohol shortly before the social confrontation. Quantitative ethological analysis revealed that alcohol prolongs "bursts" of aggressive acts and displays and disrupts communication between the aggressive animal and the opponent who defends, submits, or flees. Pharmacological modulation of the GABAA receptor with benzodiazepine agonists and neuroactive steroids results in dose-dependent biphasic changes in aggressive behavior that mimic the dose-effect function of alcohol; benzodiazepines potentiate the aggression-heightening effects of alcohol as well as the behaviorally suppressive effects; and antagonists at benzodiazepine receptors prevented the aggression-heightening effects of alcohol. The maturational and experiential origins for potentially distinctive GABAA receptor characteristics in individuals who exhibit heightened aggressive behavior await identification.

Genomic and non-genomic actions of progesterone in the control of female hamster sexual behavior.

Progesterone (P) in both the ventromedial hypothalamus (VMH) and the ventral tegmental area (VTA) is necessary to facilitate sexual receptivity in estrogen-primed hamsters. The mechanism of P may be different in the VMH and VTA, as there are many intracellular progestin receptors (PR) in the VMH but few in the VTA. Progesterone conjugated to bovine serum albumin (P-3-BSA) does not bind well to intracellular PR or permeate the surface of neuronal membranes. However, VTA application of P-3-BSA rapidly increases sexual receptivity if P has been applied earlier to the VMH. P-3-BSA is ineffective when applied to the VMH. The membrane-limited effect of P may be related to the ability of some progestins to modulate the GABAA-benzodiazepine receptor complex (GBRC). We have found that infusions of a GABAA agonist, muscimol, into the VTA enhance and a GABAA antagonist, bicuculline, inhibit receptivity. Because P itself is not highly effective at the GBRC, and since the most potent modulators of the GBRC, the 5 alpha-reduced progestins, do not bind well to PRs, progestin metabolites were applied to the VTA. Only the potent GBRC modulators facilitated sexual receptivity when applied to the VTA concurrent with P to the VMH. The reverse treatment, with a progestin metabolite implanted into the VMH, was ineffective. VTA infusions of an inhibitor of 5 alpha-reductase also attenuated behavioral estrus in hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuropharmacological characteristics of individual differences in alcohol effects on aggression in rodents and primates.

Many violent crimes have been associated with alcohol intoxication, but experimental research in laboratory animals has been largely inconclusive on alcohol effects on aggression. A focus on individual differences rather than group statistics has revealed that low doses of ethanol cause large and repeatable increases in aggressive behavior in subgroups of rodents and primates. The recent progress using in vivo neuropharmacological techniques makes it feasible to explore differences in brain mechanisms in animals that show enhanced aggression after ethanol vs those that do not. Effects of ethanol on three major neurotransmitter systems (i.e. GABA, serotonin, dopamine) are examined. Since these neurotransmitter substances are critically important in the neurobiology of various kinds of aggressive behavior in rodent and primate species, they are potential mechanisms by which ethanol alters aggressive behavior. Direct research on the relevance of the physiological interaction between ethanol and the GABA receptor suggests that at least some of the effects of alcohol on aggression involve the GABA(A)-benzodiazepine receptor complex. The role of serotonin (5-HT) will have to be newly defined in light of the findings that ethanol increases 5-HT release in several forebrain areas, in a dose range that can stimulate aggressive behavior in a subgroup of individuals. Recent in vivo studies show that acute exposure to ethanol increases dopamine release in discrete dopamine terminal areas, and that the initiation and execution of aggressive and defensive behavior are also synchronized with increased dopamine activity in these brain regions.

Progesterone and the neural mechanisms of hamster sexual behavior.

Stimulation of both the ventral medial hypothalamus (VMH) and the ventral tegmental area (VTA) by progesterone is necessary to facilitate sexual behavior in female hamsters. Recently obtained evidence indicates that progesterone exerts its behaviorally relevant actions in the VTA by acting on cell membranes. When progesterone conjugated to bovine serum albumin, which cannot permeate the cell membrane, is applied to the VTA concurrent with free progesterone to the VMH, estrogen-primed hamsters become sexually receptive. Since the reverse treatment is ineffective, this suggests that progesterone's nongenomic effects in the VTA may require concurrent genomic activation by progesterone in the VMH. The nongenomic action of progesterone on sexual receptivity may involve the GABAA receptor complex, as progestins are known to modulate this receptor complex. VTA infusions of GABAA agonists enhance, and antagonists inhibit, progesterone's effectiveness on receptivity. Finally, the behavioral effectiveness of progesterone metabolites in the VTA, concurrent with progesterone in the VMH, is consistent with their relative biochemical efficacy at the GABAA complex. These data suggest that progesterone may exert its behavioral effects in the VTA through GABAA. However, it is not yet clear whether progesterone normally acts directly on GABAA in the VTA. Progesterone may also act at some other membrane binding site and GABAA may represent an indirect mechanism for progesterone.

Alcohol, benzodiazepine-GABAA receptor complex and aggression: ethological analysis of individual differences in rodents and primates.

Research in animals has only recently been successful in reliably mimicking the long-established link between alcohol and heightened aggressive behavior. The present review highlights the large individual differences in the effects of acute low alcohol doses on aggressive behavior in rodent and primate species, paralleling the human condition. Subpopulations of both species show reliable and repeatable enhancement of aggressive behavior when administered low, acute alcohol doses. Statistical analysis of the temporal patterns of aggressive behavior indicate that alcohol prolongs aggressive bouts or "bursts" and increases the number of aggressive behaviors within each burst. However, the latency to initiate attack and the time between aggressive bursts are relatively unaltered by alcohol. These alcohol-induced increases in aggression can be potentiated by benzodiazepine agonists and prevented by antagonists. In addition, highly aggressive animals can be differentiated from nonaggressive ones at the GABAA-benzodiazepine receptor complex. These data suggest an important link between alcohol, aggression and the GABAA-benzodiazepine receptor complex.

Bicuculline infused into the hamster ventral tegmentum inhibits, while sodium valproate facilitates, sexual receptivity.

Progesterone's (P) actions on both the ventral medial nucleus of the hypothalamus (VMH) and the ventral tegmental area (VTA) are essential for sexual receptivity in female hamsters. Evidence suggests that progesterone's actions in the hamster VMH may be genomic while those in the VTA may be mediated nongenomically, via GABAA. Ovariectomized female hamsters were bilaterally implanted with cannulae aimed toward the VTA. One week after surgery, animals were SC injected with 10 micrograms estradiol benzoate (EB) and 40 h later with 200 or 500 micrograms P. At hour 43.5, 50 ng bicuculline, a GABAA antagonist, was infused into each available cannula. Control animals received 0.5 microliter sterile saline vehicle, or no infusion. At hour 44, animals were tested for sexual receptivity in an observation arena with a sexually experienced male. Histology revealed that only animals with bicuculline infused into the VTA had reduced lordosis durations compared to controls. Other animals, primed with EB and 200 micrograms progesterone, showed a facilitation of sexual receptivity after infusion into the VTA of 50 micrograms sodium valproate, a GABAA transaminase inhibitor. These results suggest that GABAA plays a necessary role in the mechanism of progesterone's actions on sexual receptivity in hamster VTA.

3 alpha-OH-DHP and 5 alpha-THDOC implants to the ventral tegmental area facilitate sexual receptivity in hamsters after progesterone priming to the ventral medial hypothalamus.

Progesterone (P) stimulation to both the ventral medial hypothalamus (VMH) and the ventral tegmental area (VTA) is necessary to facilitate sexual receptivity in female hamsters, despite the sparse population of estrogen-induced P receptors found in the VTA. Instead, P may act at neuronal membranes in the VTA. These P effects may be mediated by actions on the gamma-aminobutyric acid A-(GABAA)-benzodiazepine receptor complex (GBR). Many progestin metabolites have a greater effect in vitro on benzodiazepine binding and Cl- flux than P. If P's actions are due to metabolism to a progestin more potent at the GBR, then applying one of those progestin metabolites directly to the VTA should facilitate receptivity, if coupled with P to the VMH. To test this hypothesis three P metabolites, in decreasing order of activity at cortical synaptosome GBR, were tested: 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha-OH-DHP), 5 alpha-pregnan-3 alpha,21-diol-20-one (5 alpha-THDOC) and 5 beta-pregnan-3 alpha,21-diol-20-one (5 beta-THDOC). Ovariectomized hamsters were implanted with chronic cannulae, one aimed above the VMH and the other over the contralateral VTA. Animals were estrogen-primed and tested for sexual receptivity 4 h after a P containing insert was applied to the VMH and a metabolite containing insert was applied to the VTA. The following week the contents of the tubes were reversed; on the third week P was applied to both sites. Facilitation of receptivity occurred only when P was applied to the VMH and either P or a metabolite was applied to the VTA.(ABSTRACT TRUNCATED AT 250 WORDS)

P-3-BSA, but not P-11-BSA, implants in the VTA rapidly facilitate receptivity in hamsters after progesterone priming to the VMH.

Recent evidence suggests that progesterone (P) may have behaviorally relevant actions on neuronal membranes in the ventral midbrain. In the present experiments, we exploited the rapid time course predicted for non-genomic actions of steroid hormones. Ovariectomized hamsters were implanted with chronic guide cannulae, one aimed above the ventromedial hypothalamus (VMH) and the other over the contralateral ventral tegmental area (VTA). The following week animals were estrogen-primed (10 micrograms estradiol benzoate) and pre-tested for sexual receptivity 2 h after a P or P conjugated to the macromolecule bovine serum albumin (P-3-BSA) containing tube was applied to the VMH. P-3-BSA binds well to neuronal membranes, but does not penetrate them because of the large size of the BSA molecule. After the pre-test, the opposite hormone-containing insert was applied to the VTA and hamsters were tested again for sexual receptivity 5 min after this implantation. The following week, the contents of the tubes were reversed. Receptivity only occurred when P was applied to the VMH and 2 h later P-3-BSA was applied to the VTA; the reverse treatment was ineffective. These data indicate that P is capable of rapidly facilitating receptivity by actions on cell membranes in the VTA if P has been applied to the hypothalamus 2 h earlier. Progesterone conjugated to BSA at carbon 11 (P-11-BSA) was ineffective compared to P-3-BSA using the same paradigm. This suggests that the mechanism which responds to P in the ventral midbrain may require the 11 region.

Muscimol facilitates sexual receptivity in hamsters when infused into the ventral tegmentum.

Progestogenic stimulation of both the ventral medial nucleus of the hypothalamus (VMH) and the ventral tegmental area (VTA) within the midbrain is critical for normal receptivity in female hamsters. However, few estrogen-induced progestin receptors have been found in the midbrain. In addition, recent evidence suggests that progestin's action in the VTA is mediated nongenomically at the membrane. The present experiment investigated the possible role of GABAA receptors in mediating the effects of progesterone in this brain region. Ovariectomized female hamsters were bilaterally implanted with chronic cannulae aimed toward the ventral mesencephalon. Five days after surgery, animals were injected with 10 micrograms estradiol benzoate SC. Forty hours later, the same animals were injected with either 25 or 100 micrograms progesterone and at hour 43.5, 50 ng muscimol was infused in 0.5 microliters. Control animals received 0.5 microliters vehicle, sterile saline, or no infusion. At hour 44, animals were tested for sexual receptivity by placing them in an observation arena with a sexually experienced male for 10 min, during which lordosis duration was recorded. The following week, the same regimen was given with the alternate dose of progesterone. Histology revealed that only those animals that were infused with muscimol into the VTA had total lordosis durations that were significantly longer than the controls. Implants that missed the ventral tegmental area were much less effective. These results indicate that GABA might play a facilitatory role in enhancing the efficacy of threshold doses of progesterone. Whether this interaction is due to a direct effect of progestins on the GABAA receptor complex awaits further study.

Evidence for a non-genomic action of progestins on sexual receptivity in hamster ventral tegmental area but not hypothalamus.

Progestogenic stimulation of both the ventromedial nucleus of the hypothalamus (VMH) and the ventral tegmental area (VTA) is critical for normal receptivity in estrogen-primed hamsters. However, anatomical and biochemical studies have identified very few estrogen-induced progestin receptors in the rodent ventral midbrain. To determine whether progesterone might be working on the membrane of neurons in the VTA, progesterone 3-CMO BSA (P-3-BSA) was applied intracranially. The size of P-3-BSA makes it relatively impermeable to the cell membrane. Ovariectomized hamsters were implanted with 2 chronic cannulae, one aimed at the VMH and the other at the contralateral VTA. These animals were then estrogen-primed and tested for sexual receptivity after progesterone-containing tubes were inserted just dorsal to the VMH and P-3-BSA inserts were applied above the VTA. The following week, the hamsters were tested again with the contents of the inserts reversed. Animals with progestogenic stimulation to the VMH and P-3-BSA to the VTA were receptive yet those with P-3-BSA to the hypothalamus and progesterone to the VTA were not receptive. These data suggest that progesterone is capable of facilitating sexual receptivity within the VTA by actions on the cell membrane. The non-genomic effects in the VTA require concurrent genomic activation by progesterone within the hypothalamus.

Alcohol and "bursts" of aggressive behavior: ethological analysis of individual differences in rats.

A quantitative ethological analysis of rodent aggression was performed in order to characterize the aggression-heightening effects of alcohol in certain individuals. In dyadic confrontations, a resident rat pursues, threatens and attacks an intruder, who reacts with defensive, flight and submissive behaviors. The behavioral data from five series of experiments conducted from 1984 through 1989 were subjected to a lag sequential analysis that identified highly predictable sequences of aggressive behavior, and to interval analysis that delineated a burst pattern of aggressive behavior. These analyses revealed a distinct behavioral sequence of pursuit----sideways threat----attack bite----aggressive posture that occurs in bursts with an inter-event interval of less than 6.6 s. In the total population, alcohol heightened attack behavior at low acute doses (0.1, 0.3, 1.0 g/kg) in 47% of the animals (n = 44), suppressed reliably attack behavior in another 25% (0.1-3.0 g/kg; n = 23) and had unreliable effects in the remaining 28% (n = 24). The peak enhancement of aggressive behavior was seen over more than a log cycle of alcohol doses (0.1, 0.3 or 1.0 g/kg) in different individuals. In an additional group of rats (n = 20), individuals were identified according to whether or not acute low alcohol doses enhanced or suppressed the frequency of attack bites. In the subgroup of five rats who doubled their attack frequency upon acute alcohol challenge, this aggression-heightening effect was confirmed on repeated occasions. The aggression-heightening effects of alcohol were seen during the high-rate interactions in the initial phase of the confrontation and particularly during the lower level of fighting later on. Regardless of alcohol dose and subgroup, the highly predictable sequence of pursuit----sideways threat----attack bite----aggressive posture remained intact as long as the individual was able to fight. The present analysis identifies those individuals in whom low alcohol doses increase the frequency of attack behavior, the number of aggressive elements in bursts and particularly the "time in burst". Alcohol produces these changes without altering the latency to initiate aggressive behavior, the rate of aggressive behavior within a burst or the number of bursts in an encounter. Alcohol may lengthen aggressive bursts by preventing termination of longer aggressive sequences rather than by altering the initiation of this behavior.

Ventral tegmental lesions impair sexual receptivity in female hamsters.

The ventral mesencephalon appears to be one of the sites of progesterone action in the control of sexual receptivity in female hamsters. The behavioral response to systemic progesterone was assessed in female hamsters following electrolytic lesions of portions of the ventral mesencephalon. Adult female hamsters were ovariectomized and pretested for sexual receptivity, then were given bilateral lesions aimed at the region of the ventral mesencephalon where progesterone implants have been shown to facilitate receptivity. Lesions were produced by stereotaxically lowering an electrode and applying anodal direct current of 1-2 mA for 5-20 seconds. One week later the hamsters were injected with estrogen followed 44 h later by progesterone. They were then tested for sexual receptivity. After this test, their brains were removed and histologically prepared. Lesion location was determined and lesion size was quantified with a digitizing pad. Lesions which were centered in and destroyed much of the ventral tegmental area produced the greatest lordosis impairments. Mesencephalic lesions which did not bilaterally damage the ventral tegmental area had little effect. These results support the hypothesis that the ventral mesencephalon, particularly the ventral tegmental area, is an important site for the facilitative action of progesterone on sexual receptivity in estrogen-primed female hamsters.

Intravenous administration of progesterone and the onset of receptivity in female hamsters.

Progesterone-facilitated receptivity is believed to be a genomically mediated event. However, in contrast to estrogen, progesterone's effects occur rapidly. This experiment was designed to examine the temporal onset of receptivity in hamsters following intravenous (IV) administration of progesterone. Ovariectomized female hamsters were tested for their responsiveness to 10 micrograms estradiol benzoate (EB) plus 0, 50, or 200 micrograms progesterone, administered subcutaneously (SC). The hamsters were tested for sexual receptivity at 0.5, 1, 1.5, 2, 3 and 4 h. Three days later they were fitted with jugular catheters. Two days after catheter implantation they received 10 micrograms EB SC; 48 h later they were tested for receptivity and then received an IV injection of 0, 50, or 200 micrograms progesterone in 0.2 ml propylene glycol. Following the IV P injection the animals were again tested at 0.5, 1, 1.5, 2, 3 and 4 h. Progesterone administration (either SC or IV) resulted in an increase in total lordosis duration (TLD) over time. TLD had significantly increased from the pre-progesterone levels by 2 h after 50 micrograms progesterone IV. In contrast, 50 micrograms progesterone SC did not cause an increase in TLD until 3 h postinjection. Moreover, in comparison to SC administration, the effects of IV progesterone were short-lived; TLD was significantly decreased by 4 h after injection. Following 200 micrograms progesterone, the latency to respond was shorter than with 50 micrograms progesterone (1.5 vs. 2 h). There was no difference in the onset of receptivity as a function of route of administration at the 200 micrograms dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethanol-induced depression of aggression in mice antagonized by hyperbaric exposure.

The present study investigated the effect of hyperbaric exposure on ethanol-induced depression of aggressive behavior measured by resident-intruder confrontations. Adult male CFW mice (residents) were paired with females and housed together for 26 days. Then, resident mice were intubated with either ethanol (2 g/kg) or water (20 ml/kg) and were exposed to 1 atmosphere absolute (ATA) air, 1 ATA helium oxygen (heliox) or 12 ATA heliox using a within-subjects counterbalanced design. Thirty minutes after intubation an intruder was introduced. Ethanol significantly decreased aggressive behaviors (attack latency, attack bites, sideways threats, tail rattles and pursuit) in 1 ATA-treated animals. Pressure completely antagonized the depression of aggression induced by ethanol. Ethanol alone and pressure alone did not significantly affect nonaggressive behaviors. There were no statistically significant differences between groups in blood ethanol concentrations 50 minutes after intubation. These results suggest that ethanol's effects on aggressive behavior result from the same membrane actions leading to loss of righting reflex, depression of locomotor activity, tolerance and dependence.

Facilitation of sexual receptivity in hamsters by simultaneous progesterone implants into the VMH and ventral mesencephalon.

Intracranial implantation experiments have shown that the ventromedial hypothalamus (VMH) is the most sensitive site for the facilitation of female sexual behavior by progesterone in estrogen-primed rats. However, similar implantation techniques have been much less successful in hamsters. Several lines of evidence indicate that both hypothalamic and midbrain structures are important for hamster lordosis. Therefore we compared the effect of progesterone (P) implants administered simultaneously to VMH and ventral midbrain on opposite sides of the brain to the effects of bilateral implants to each of these sites separately. Ovariectomized female hamsters were stereotaxically implanted with 24-gauge thin-wall guide tubes according to one of five patterns. Bilaterally symmetrical cannulae were aimed at VMH or ventral mesencephalon (vMES) or asymmetrical implants were aimed at one of the following pairs of sites, on opposite sides of the brain: VMH-vMES, VMH-preoptic area (VMH-POA), or anterior hypothalamus-anterior mesencephalon (AH-aMES). After recovery from surgery, females were primed with 10 micrograms estradiol benzoate and given pellets of P or cholesterol through a 30-gauge injector in the targeted sites. Latency, frequency, and duration of lordosis were recorded in 10-min tests with sexually active male hamsters. Sexual receptivity was significantly facilitated by simultaneous contralateral P implants into the VMH-vMES. P implants in any other combination of sites did not significantly facilitate lordosis compared to cholesterol control implants, nor did bilateral administration of this dose of P in either VMH or vMES have a reliable effect. The results support the hypothesis that P action is required in both VMH and vMES to reliably stimulate receptivity in hamsters.

Sexual differentiation and the effects of alcohol on aggressive behavior in mice.

Male and female mice are differentially sensitive to the effects of alcohol on aggressive behavior. We investigated the role of testosterone during sexual differentiation in determining sex differences in alcohol effects on aggression. On the day of birth male mice were castrated or sham-operated. Neonatal female mice were injected with 250 micrograms of testosterone propionate (TP) or the oil vehicle. At approximately 75 days of age the mice which had not been gonadectomized at birth were gonadectomized. Control males and androgenized female mice then received 7.5 mm Silastic capsules containing testosterone, SC. Aggressive behavior toward an intruder was assessed following administration of ethanol (0.1-3.0 g/kg) or water, PO. Neonatally sham-gonadectomized male mice had a significant increase in aggressive behavior following administration of 1.0 g/kg alcohol, with no significant suppression of aggression at 3.0 g/kg. Neonatally androgenized female mice showed neither the male-typical response to adult testosterone and alcohol, nor did they show the female-typical response. Neonatally gonadectomized males showed an alcohol dose response curve that was similar to that of androgenized females. Postnatal testosterone did not appear to completely determine the male- and female-typical responses to alcohol on aggression. The critical period for this sexually dimorphic response to alcohol and testosterone may be primarily prenatal.

Facilitation of sexual receptivity by hypothalamic and midbrain implants of progesterone in female hamsters.

In the first experiment, ovariectomized female hamsters were stereotaxically implanted with bilateral guide cannulae aimed at the medial preoptic area (POA), ventromedial hypothalamus (VMH), or ventral tegmentum (VTA). The following week these females were injected SC with 10 micrograms estradiol benzoate (EB) and then had 27-gauge cannulae containing crystalline progesterone inserted through the guide tubes. Sexual receptivity was observed in 3 of 11 animals with VMH implants of progesterone, in 2 of 10 with VTA progesterone, but in none with POA implants. In the second experiment, the amount of intracranial progesterone was increased by mechanically expelling a 1.5 micrograms progesterone pellet from the tip of each cannula insert. This treatment facilitated receptivity in 10 of 20 hamsters with VTA implants and in 9 of 32 VMH-implanted animals. This induction of receptivity required approximately 2 hr. Progesterone pellets in the POA, mammillary region, and lateral mesencephalon were generally ineffective. In hamsters, progesterone into either the VMH or the VTA is sufficient to facilitate receptivity, although neither site is highly sensitive to progesterone. These results differ from those in recent studies in rats and this difference may reflect important species differences in the control of lordosis.