Chronic administration of propranolol impairs inhibitory avoidance retention in mice

Adrenergic systems are importantly involved in memory storage processes. As such, agents that alter adrenergic receptors, such as "beta-blockers," also alter memory storage. However, the anxiety literature cautions that beta-adrenergic receptor antagonists, such as propranolol, may have different behavioral effects with acute vs chronic dosing. The effects of chronic propranolol specifically on memory modulation are unknown. This study was designed to evaluate the effects of chronic propranolol on retention for an aversive task, in which there is endogenous adrenergic activation. Adult male ICR mice were given daily injections of one of four doses of propranolol (2, 4, 8, and 12 mg/kg) or 0.9% NaCl vehicle for 15 days prior to, and continuing during, behavioral tests of exploration and retention. Exploratory behavior, as an index of anxiety level, was measured in a conventional elevated plus-maze, whereas retention of an aversive experience was measured in a step-through inhibitory avoidance apparatus. Sensitivity to aversive footshock was also evaluated. Compared to controls, propranolol-treated mice showed a dose-dependent decrease in retention for the inhibitory avoidance task, but no effect on anxiety on the plus-maze or on footshock sensitivity. Taken together with results from previous studies, it is apparent that propranolol can have different behavioral effects when administered acutely vs chronically, and its chronic effects significantly impair memory storage processes. Since these drugs are typically used chronically, and often in older adults, they could contribute to functional memory impairments.     

Effects of pretraining intrastriatal administration of p-chloroamphetamine on inhibitory avoidance

Pretraining systemic administration of p-chloroamphetamine (PCA) consistently produces retention deficits of inhibitory avoidance. This drug causes a widespread acute release of serotonin from cerebral neuronal terminals, but it is not known where in the brain PCA exerts its disruptive cognitive effects. The present experiment was aimed at determining whether the striatum is a site of action of this drug. PCA (5 microg) was infused, bilaterally, into the striatum of rats at 30, 15, or 5 min before training of inhibitory avoidance, and retention of the task was measured 24 h later. An inversely related time-dependent deficit was found. Together with the results from appropriate control groups, this result strongly suggest that systemic PCA produces its reported cognitive effects, at least in part, through its pharmacological action within the striatum.     

Oral administration of guanosine impairs inhibitory avoidance performance in rats and mice

Extracellular guanine-based purines, mainly the nucleoside guanosine, have recently been shown to exert neuroprotective effects, which seem to be related to antagonism of the glutamatergic system. In this study, we investigated the effects of acute oral administration of guanosine on inhibitory avoidance task in rats and mice. We also studied its effects on locomotor activity, anxiety-related behaviors and mechanisms of action involving the purinergic system. Guanosine (2.0 and 7.5mg/kg, per os), administered 75min pretraining, dose-dependently impaired retention of the inhibitory avoidance task in rats and mice, an effect not prevented by the adenosine receptor antagonist caffeine. Guanosine presented no effects on locomotor activity and anxiety-related behaviors. This amnesic effect of guanosine may be compatible with inhibition of glutamatergic system and seems to be not mediated by adenosine.     

Open-field and avoidance behavior after neostriatal lesions in male and female rats.

The behavioral effects of lesions of the anterodorsal or posteroventral parts of the caudate-putamen were studied in adult male and femle rats that were gonadectomized or left untreated prior to brain surgery. Anterodorsal (ADC) lesions consistently impaired acquistion of one-way avoidance behavior and tended to interfere with the development of a two-way avoidance response; comparable effects were observed in gonadectomized and intact animals of both sexes. By contrast, ADC lesions increased activity in the open field only in intact females and increased rearing only in ovariectomized females. Posteroventral caudate (PVC) lesions caused transient aphagia and adipsia in both sexes but did not consistently affect open-field activity or the acquistion of one-way avoidance responses by either sex. These lesions profoundly impaired acquistion of shuttle box avoidance responses by intact males. By contrast, castrated males and intact and ovariectomized females with PVC lesions avoided normally in the shuttle box. The present results suggest that localization of behavioral functions within the striatum differs with the sex of the subject, in part because of activational effects of gonadal hormones.     

Genotype modulates prenatal stress effects on aggression in male and female mice

Prenatal stress (heat and restraint) significantly increased postpartum aggression (proportion of animals fighting and/or the intensity of the behavior) in C57BL/6J female mice and reduced the behavior in DBA/2J females. For intermale aggression, prenatal stress increased the behavior (intensity of aggression) in C57BL/6J males but did not affect aggressive behavior in DBA/2J animals. Infanticidal behavior (the killing of young) exhibited by male mice was not influenced by prenatal stress in either strain. Relative anogenital distance measurements in neonates at birth did not serve as a reliable predictor of strain variation in prenatal stress effects. Prenatal stress did not influence this measure of prenatal androgen exposure in DBA/2J or C57BL/6J females. For males, prenatal stress elevated relative anogenital distance in C57BL/6J mice and decreased this measure in DBA/2J animals. Prenatal stress effects on aggressive behavior in male and female mice therefore depend upon genotype. Strain-dependent differences may be modulated by differences in endocrine reactivity to prenatal stress/and or differential central neural tissue sensitivity to hormones.     

Maternal aggression in mice and rats towards male and female conspecifics

Although postpartum aggression is primarily studied in laboratory mice and rats, it is unclear how the two species compare in terms of the factors associated with peak levels of aggressive behavior. Using the same experimental protocol, we assessed the relative effect of intruder sex and time since parturition on the frequency of maternal aggression in Long-Evans rats and CFW mice. Females were studied for 2 consecutive cycles of pregnancy and lactation. During the first lactation, aggression was tested 2 times per week for 3 weeks in order to select animals that attacked at least once. During the second lactation, both pup care and aggressive behavior were assessed in detail. Testing occurred twice in each lactation week, with postpartum days 1–7, 8–14, and 15–21 considered weeks 1, 2, and 3, respectively. Maternal behavior towards 3 pups was observed for 5 minutes, followed by a confrontation with an intruder. Lactating females encountered female intruders once per week, and male intruders in the alternate weekly test. The same behaviors were measured in the 2 species, except for the tail rattle exhibited by mice and the aggressive posture shown by rats. Lactating rats and mice show similar decreases in pup care behavior as lactation progresses in time; yet the factors associated with peak levels of aggression differ between species. In Long-Evans rats, female intruders receive more attacks, threats, and aggressive postures than males. Frequency of attack bite and sideways threat declines in each passing week of lactation. Lactating mice are more aggressive toward male intruders throughout the lactation period. Mice still attack and threaten during the third week of lactation, but less often in comparison to the first week. Therefore, peak levels of aggression vary in mice and rats both as a function of intruder sex and lactation week.     

Effects of ritanserin on offense and defense in male mice

Effects of ritanserin on agonistic behavior of isolated mice exhibiting aggressive or nonaggressive behavioral strategies were studied in pair-wise encounters with group-housed opponents. An ethological approach to behavioral scoring is adopted, which allows for examination of the profiles of individual subjects. Although the data generally support the view that ritanser in has little effect on offense or defense in male mice, the stimulation of pre-aggressive behavior (threats, alerts, tail rattles) was detected in some nonaggressive mice. © 1995 Wiley-Liss, Inc.     

Effects of stress on nonassociative learning processes in male and female rats

In this study we assessed habituation and sensitization of the acoustic startle response (ASR) to discern whether intense, inescapable stress affects nonassociative learning differently in male and female rats. Rats were inescapably stressed 2 hours per day over 3 consecutive days. ASR magnitudes were measured at several times post-stress (1, 4, 8, and 15 days after cessation). Females generally showed greater ASR magnitudes (compared to males), but both sexes exhibited short and long-term habituation across the testing days. ASR magnitudes were only affected by stress in male subjects. The effect in males was an increase in short-term sensitization of the ASR on post-stress day-4. The results suggest that stressed males and females react differently to ASR testing, in that stress males appear to develop an exaggerated ASR response over repeated test sessions due to short-term sensitization. The source of the short-term sensitization is discussed with regards to possible stress-induced enhanced contextual learning during ASR testing on post-stress day-1.     

Role of muscarinic M1 receptors in inhibitory avoidance and contextual fear conditioning

The objective of the present study was to observe the effects of pre-training or post-training administration of dicyclomine, a M1 muscarinic antagonist, on inhibitory avoidance (IA) and contextual fear conditioning (CFC) and to investigate if the effects observed with the pre-training administration of dicyclomine are state-dependent. For each behavioral procedure (IA and CFC) groups of Wistar male rats were treated with saline or dicyclomine either 30 min before training (pre-training), immediately after training or 30 min before training/30 min before test (pre-training/pre-test). The animals were tested 24 h after training. The acquisition of IA and CFC was impaired by pre-training administration of dicyclomine. The consolidation of both tasks was not affected by dicyclomine given immediately after training. Pre-training/pre-test administration of dicyclomine impaired both tasks, an effect similar to that observed in the group which only received pre-training administration. Pre-test treatment induced dissociation between both tasks, impairing CFC retrieval, without interfering with the animals avoidance response. These results show that the dicyclomine did not affect IA and CFC consolidation, suggesting specific involvement of M1 muscarinic receptor only in acquisition these tasks, and these effects was not state-dependent. However, it is possible that the retrieval of these tasks may be mediated, at least in part, by different neurochemical mechanisms and may be dissociated by dicyclomine.     

Effects of neonatal cyproterone acetate administration on isolation-induced fighting behavior and mounting behavior in male and female TO strain albino mice

The effects of a single dose (1 mg) of cyproterone acetate administered on either day 1 or day 20 of life on the adult behaviors of male and female TO strain albino mice were studied. The mice were tested both in a “standard opponent”-type situation and in a similar test using a hormonally primed receptive female, after being gonadectomized and maintained with testosterone propionate as adults. Neonatal treatment with this compound had little effect on subsequent fighting behavior in either sex, but clear evidence was produced that this treatment masculinized the sexual behavioral potentialities of the females, an effect which was apparent in animals which had been injected on either day 1 or day 20 of life. Indications were obtained that females treated neonatally with cyproterone acetate were capable of differentiating between the male and female “opponents” in a manner similar to the male. The effects of this treatment on fighting behavior consequently appear to be dissimilar to the effects of neonatal castration in this species. However, the effects on mounting behavior in the females, evidenced in adulthood, seem Likely to be a consequence of the weak androgenic properties of the antiandrogen. The administration of cyproterone acetate neonatally appears to have a more dramatic effect on the adult weights of endocrine organs in females than in mates.     

Differential roles of hippocampal metabotropic glutamate receptors 1 and 5 in inhibitory avoidance learning

Group I metabotropic glutamate receptors (mGlu1 and 5) have been implicated in synaptic plasticity and learning and memory. However, much of our understanding of how these receptors in different brain regions contribute to distinct memory stages in different learning tasks remains incomplete. The present study investigated the effects of the mGlu5 receptor antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), and mGlu1 receptor antagonist, (S)-(+)-alpha-amino-4-carboxy-2-methylbenzene-acetic acid (LY 367385) in the dorsal hippocampus on the consolidation and extinction of memory for inhibitory avoidance learning. Male, Sprague-Dawley rats were trained in a single-trial step-down inhibitory avoidance task. MPEP, LY 367385 or saline were infused bilaterally into the CA1 region immediately after training or immediately after the first retention test which was given 24h after training. Rats receiving MPEP (1.5 or 5.0 microg/side) or LY 367385 (0.7 or 2.0 microg/side) infusion exhibited a dose-dependent decrease in retention when tested 24h later. MPEP was ineffective while LY 367385 significantly attenuated extinction when injected after the first retention test using an extinction procedure. These findings indicate a selective participation of hippocampal group I mGlu receptors in memory processing in this task.     

Effects of female odors on the sexual behavior of male hamsters

A series of experiments was undertaken to investigate the effects of removal of several scent glands and scent-producing organs of female hamsters on the copulatory performance of male hamsters. In the first experiment it was shown that males engage in less copulatory activity toward females lacking vaginal secretions than toward females with these odors. Eliminating visual cues by observing pairs under infrared illumination did not change the performance of males toward these two kinds of females. The results of Experiment 2 indicated the importance of flank, ear, and Harderian glands as well as vaginal secretions--males showed the highest levels of copulatory behavior toward females with a full complement of odors and the lowest levels toward those lacking three of four sources of scent. Similar results were obtained in the third experiment in which anesthetized females were used as stimulus animals to increase the importance of chemical cues and to reduce variability due to the behavior of females. The sexual behavior of males was greatest toward females with all sources of scent present, lower toward those lacking vaginal secretions, and still lower toward those lacking vaginal secretions and other sources of odors. In the fourth experiment we asked whether any one of the nonvaginal scent glands was particularly important in stimulating male sexual behavior, but we found no differences in male performance toward females that lacked vaginal secretions or that in addition lacked one of the other scent glands. In the fifth experiment males displayed higher levels of sexual behavior toward vaginectomized females than toward vaginectomized females that had been deodorized by a cleaning procedure, again indicating the importance of nonvaginal odors in stimulating copulatory performance. Thus these experiments demonstrate the importance of vaginal secretions in the sexual arousal of male hamsters, a role for nonvaginal odors in sexual arousal of males, and the lack of necessity of these odors for male copulatory behavior. These results have implications for theories of olfactory communication in mammals and for interpretations of experiments in which lesions of the olfactory system lead to deficits in male copulatory performance.     

Infanticide and maternal aggression: Synchrony of male and female reproductive strategies in mice

Thirty-six percent of male mice from three strains attacked newborn pups sired by another male. No male attacked its own offspring. Females did not show differential aggression toward males likely (strangers) or unlikely (sires) to attack their pups. Both forms of aggression were unaffected by housing in rooms which did or did not contain the aggression targets. The three strains differed in strength of maternal aggression but not in the incidence of infanticide. Females showed more aggression when mated with males of the same, rather than a different, strain but no differences with intruders of the same or a different strain. Infanticide by males is best viewed as a postcopulatory, intermale-competition strategy, and maternal aggression as a counter strategy.     

Effects of posttraining treatments in the posterior cingulate cortex on short- and long-term memory for inhibitory avoidance in rats

Adult male Wistar rats were bilaterally implanted with indwelling cannulae in the caudal region of the posterior cingulate cortex. After recovery, animals were trained in a step-down inhibitory avoidance task (3.0-s, 0.4-mA foot shock) and received, right after training, a 0.5-microl infusion of vehicle (phosphate-buffered saline, pH 7.4), of the GABA(A) receptor agonist muscimol (0.1 or 0.5 microg), of the cAMP-dependent protein kinase (PKA) stimulant Sp-cAMPS (0.1 or 0.5 microg), or of the PKA inhibitor Rp-cAMPS (0.1 or 0.5 microg). Animals were tested twice, 1.5 h and, again, 24 h after training, in order to examine the effects of these agents on short- and long-term memory, respectively. Muscimol (0.5 but not 0.1 microg) hindered retention for both short- and long-term memory (p <.05). Rp-cAMPS (0.1 or 0.5 microg) hindered retention for short-term memory (p <.05). In addition, these animals showed lower, but not significantly lower, latencies than controls in the test session for long-term memory (p >.10). A trend toward an amnesic effect on long-term memory was also observed after Sp-cAMPS infusion at 0.1 microg (p <.10). These results show that strong stimulation of GABAergic synapses in the caudal region of the rat posterior cingulate cortex right after training impairs short- and long-term memory (the latter less dramatically). The same occurs by inhibiting PKA activity with regard to STM and possibly to LTM.     

Effects of female presence on intrasexual aggression in male lizards,Podarcis hispanicus

Resource value and expected gain in reproduction may affect motivation to fight and the likelihood of winning. Previous experiments have showed that males increase their fighting effort when defending a territory that contains females. However, we hypothesized that for an intruding lizard, the value of a new territory may be lower if he already has a female in his own territory, and consequently, aggressivity should be lesser than if he has no access to any female. We staged encounters between males of the lizard Podarcis hispanicus in outdoor terraria to analyze the outcome and detailed behaviors involved in agonistic interactions in the presence or absence of a female in the terraria of resident and intruders. Our results showed that when a female was present, the level of aggressivity of the resident male was higher; the probability of winning the contest also increased, but only if the intruding male had no females in his own terraria. In contrast, when the intruding male was also the owner of another territory containing a female, residents were less aggressive. We suggest that the lack of information on the reproductive state of an unfamiliar female may be enough to decrease fighting motivation of an intruding male, if he has more expectations of success with his own familiar female. We conclude that differences in expected reproductive success with different females may help to decide the outcome of conflicts between males quicker and cheaper. Aggr. Behav. 28:491–498, 2002. © 2002 Wiley‐Liss, Inc.