Robert L. Meisel

The Effects of Energy-Rich Diets on Discrimination Reversal Learning and on BDNF in the Hippocampus and Prefrontal Cortex of the Rat

Male rats received normal chow or high-fat diets rich in dextrose (HFD) or sucrose (HFS). Half of the rats received 90-day unrestricted access to their diet prior to training, whereas the other half were food restricted throughout the study. We evaluated the effects of these dietary manipulations on discrimination and reversal performance and on post-training levels of brain-derived neurotrophic factor (BDNF) in the prefrontal cortex and the ventral and dorsal hippocampus. Neither diet nor restriction condition affected discrimination acquisition. However, prior unrestricted access to the HFD diet impaired discrimination reversal learning and reduced BDNF in the prefrontal cortex and ventral hippocampus. Also, rats given the HFD diet responded more than controls to the previously rewarded cue at the outset of discrimination reversal. The results suggest that consumption of the HFD diet may have had enduring effects on learning processes, some of which may contribute to the control of intake regulation.

A microdialysis study of ventral striatal dopamine during sexual behavior in female Syrian hamsters

Microdialysis was used to study the effects of exposure to a male hamster on extracellular concentrations of dopamine, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA) in the ventral striatum of ovariectomized female Syrian hamsters pretreated with either estradiol and progesterone, or a similar regimen of oil injections. The hormone-treated females showed high levels of lordosis throughout the hour of exposure to the male. In hormone-treated females, there was a rapid elevation of dialysate dopamine within the first 15 min of exposure to the male. Dialysate dopamine gradually declined over the next 45 min, though remaining significantly above baseline during the entire period of exposure to the male. None of the oil-treated females showed any indication of lordosis, and the addition of the male produced only a small increase in dopamine at 30 min, after which dopamine returned to pre-male basal levels. DOPAC, HVA, and 5-HIAA were all elevated following introduction of the male for both groups of females. These results suggest that ovarian hormones modulate the responsivity of ventral striatal dopamine to incentive stimuli associated with mating behavior in females, although extracellular levels of dopamine in the ventral striatum do not seem to be directly coupled to the display of lordosis.

Conditioned place preference in female hamsters following aggressive or sexual encounters

Prior studies have demonstrated the utility of conditioned place preference procedures for examining the motivational or rewarding properties of behavior. The purpose of this experiment was to assess whether female Syrian hamsters would show evidence of conditioned place preference for aggression or sexual behaviors. Weekly conditioning sessions were conducted for three groups of female hamsters for 5 weeks. One group of female hamsters engaged in sexual activity with a male hamster in the gray compartment of a place preference apparatus. A second group of females experienced aggressive interactions with a male when placed together also in the gray compartment. Females in each of these conditioning groups were placed alone in the white compartment within 1 h of the behavioral interactions. A control group of hormone-treated females was placed alone in both compartments of the apparatus. Following the conditioning sessions, all females were given free access to the conditioning apparatus. Females with prior sexual or aggressive experience spent significantly more time in the gray compartment than they did before conditioning. Control females did not show any significant change in their preference for either compartment of the apparatus. The results suggest that female hamsters prefer an environment associated with the prior rewarding properties of sexual or aggressive interactions.

Sexual Behavior Induction of c-Fos in the Nucleus Accumbens and Amphetamine-Stimulated Locomotor Activity Are Sensitized by Previous Sexual Experience in Female Syrian Hamsters

Dopamine transmission in the nucleus accumbens can be activated by drugs, stress, or motivated behaviors, and repeated exposure to these stimuli can sensitize this dopamine response. The objectives of this study were to determine whether female sexual behavior activates nucleus accumbens neurons and whether past sexual experience cross-sensitizes neuronal responses in the nucleus accumbens to amphetamine. Using immunocytochemical labeling, c-Fos expression in different subregions (shell vs core at the rostral, middle, and caudal levels) of the nucleus accumbens was examined in female hamsters that had varying amounts of sexual experience. Female hamsters, given either 6 weeks of sexual experience or remaining sexually naive, were tested for sexual behavior by exposure to adult male hamsters. Previous sexual experience increased c-Fos labeling in the rostral and caudal levels but not in the middle levels of the nucleus accumbens. Testing for sexual behavior increased labeling in the core, but not the shell, of the nucleus accumbens. To validate that female sexual behavior can sensitize neurons in the mesolimbic dopamine pathway, the locomotor responses of sexually experienced and sexually naive females to an amphetamine injection were then compared. Amphetamine increased general locomotor activity in all females. However, sexually experienced animals responded sooner to amphetamine than did sexually naive animals. These data indicate that female sexual behavior can activate neurons in the nucleus accumbens and that sexual experience can cross-sensitize neuronal responses to amphetamine. In addition, these results provide additional evidence for functional differences between the shell and core of the nucleus accumbens and across its anteroposterior axis.

6 – Hormonal Basis of Social Conflict and Communication

Publisher Summary There is a substantial body of data on the interactions among hormones, reproductive behavior, and communicative behavior. However, significantly less is known about how hormones regulate social conflict and the communicative behaviors that are involved in influencing social relationships This chapter focuses on the hormonal regulation of social conflict and communication in Syrian (sometimes called golden) hamsters. Social behavior and its hormonal regulation have been studied in Syrian hamsters since the 1950s. Unlike many other species, both male and female hamsters are highly aggressive, and the behaviors engaged in during social conflict are readily observable and easily quantified. The severity of these encounters (in terms of bites or tissue damage) is usually quite low, and dominance relationships are often formed with relatively little overt aggression. These relationships are usually established very rapidly and remain stable over time. Hamsters also exhibit a variety of communicative behaviors that are easily quantified and that have been investigated extensively. As such, hamsters represent a comparatively simple animal model for the study of social conflict and communication.

Opposite Effects of mGluR1a and mGluR5 Activation on Nucleus Accumbens Medium Spiny Neuron Dendritic Spine Density

The group I metabotropic glutamate receptors (mGluR1a and mGluR5) are important modulators of neuronal structure and function. Although these receptors share common signaling pathways, they are capable of having distinct effects on cellular plasticity. We investigated the individual effects of mGluR1a or mGluR5 activation on dendritic spine density in medium spiny neurons in the nucleus accumbens (NAc), which has become relevant with the potential use of group I mGluR based therapeutics in the treatment of drug addiction. We found that systemic administration of mGluR subtype-specific positive allosteric modulators had opposite effects on dendritic spine densities. Specifically, mGluR5 positive modulation decreased dendritic spine densities in the NAc shell and core, but was without effect in the dorsal striatum, whereas increased spine densities in the NAc were observed with mGluR1a positive modulation. Additionally, direct activation of mGluR5 via CHPG administration into the NAc also decreased the density of dendritic spines. These data provide insight on the ability of group I mGluRs to induce structural plasticity in the NAc and demonstrate that the group I mGluRs are capable of producing not just distinct, but opposing, effects on dendritic spine density.

Dopamine receptor antagonists attenuate conditioned place preference following sexual behavior in female Syrian hamsters

We assessed the effects of the dopamine D2 receptor antagonists, sulpiride and raclopride, on conditioned place preference produced by sexual behavior in female Syrian hamsters. Female hamsters treated with sulpiride or raclopride showed high levels of sexual behavior (lordosis) that were equivalent to control females receiving vehicle injections. The degree of place preference conditioning for sulpiride-treated females was marginally reduced, whereas females treated with raclopride showed no evidence of conditioning. These results indicate that conditioned place preference is a useful means for probing the appetitive components of female sexual behavior, and that dopamine D2 receptors are involved in this appetitive process.

c-Fos expression in female hamster brain following sexual and aggressive behaviors

The goal of these experiments was to use c-Fos immunocytochemistry to determine areas of the female hamster brain that are active during lordosis and aggression. Ovariectomized hamsters were given (i) estradiol and progesterone, plus a lordosis test, (ii) estradiol and progesterone, but no lordosis test, (iii) oil, plus an aggressive behavior test, or (iv) oil, but no behavior test. Results showed that following lordosis, there was increased c-Fos expression in the medial bed nucleus of the stria terminalis, medial accumbens, medial preoptic nucleus, paraventricular nucleus and medial amygdala. Following a single aggression test, c-Fos was significantly increased only within the medial amygdala. There was no effect of lordosis or aggression on c-Fos expression within the lateral or central ventromedial hypothalamus, suprachiasmatic nucleus or dorsal midbrain central gray. In a second experiment, ovariectomized female hamsters were given (i) repeated aggressive experience, (ii) a single aggression test or (iii) no aggression test. Because some females were not aggressive towards males, they became a separate group post hoc. The number of cells expressing c-Fos was higher in the medial preoptic nucleus and medial amygdala of females given a single aggressive test and in non-aggressive females vs control females. Females given prior aggressive experience showed higher c-Fos expression only in the medial preoptic nucleus. These results demonstrate that increased neural activation in several forebrain nuclei is seen after sexual or aggressive behaviors in female hamsters. However, because the pattern of c-Fos staining in the non-aggressive females was similar to the pattern in aggressive females, this questions previous conclusions regarding the behavioral specificity of these effects and suggests instead that such activation is common to social interactions in general.

Effects of serotonin 1A or 1B receptor agonists on social aggression in male and female Syrian hamsters

Numerous studies have demonstrated that activation of serotonin 5-HT1A or 5-HT1B receptor decreases aggression in male mammals. To determine whether female mammals also show decreased aggression in response to 5-HT1A or 5-HT1B activation, we assessed the effects of the serotonin receptor agonists 8-OH-DPAT (5-HT1A) and CGS-12066A (5-HT1B) on aggression in female Syrian hamsters. Female Syrian hamsters were tested for interfemale aggression 2 days before and 15 min after receiving intracerebroventricular infusions of 8-OH-DPAT (5, 10, 20 microg) or CGS-12066A (5, 10, 20 microg). Neither drug affected aggression as measured by the latency and frequency of attacks or uprights, although the highest dose of 8-OH-DPAT increased general activity. For male hamsters, intraventricular infusions of 10 microg of 8-OH-DPAT essentially eliminated aggression, whereas 5 microg of 8-OH-DPAT or 20 microg of CGS-12066A were without effect. Systemic treatment with 8-OH-DPAT (1 mg/kg body weight) did reduce aggression in females, although there was an attendant increase in symptoms of nonspecific serotonergic activity. There were no behavioral effects of systemic CGS-12066A (4 mg/kg body weight) on female hamsters. These results indicate that there may be sex differences in the neurochemical regulation of aggression and point to a need for more studies directed at this issue.

Sexual Experience in Female Rodents: Cellular Mechanisms and Functional Consequences

The neurobiology of female sexual behavior has largely focused on mechanisms of hormone action on nerve cells and how these effects translate into the display of copulatory motor patterns. Of equal importance, though less studied, are some of the consequences of engaging in sexual behavior, including the rewarding properties of sexual interactions and how sexual experience alters copulatory efficiency. This review summarizes the effects of sexual experience on reward processes and copulation in female Syrian hamsters. Neural correlates of these sexual interactions include long-term cellular changes in dopamine transmission and postsynaptic signaling pathways related to neuronal plasticity (e.g., dendritic spine formation). Taken together, these studies suggest that sexual experience enhances the reinforcing properties of sexual behavior, which has the coincident outcome of increasing copulatory efficiency in a way that can increase reproductive success.