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1.
The hypothalamic neuropeptide orexin (hypocretin) mediates reward related to drugs of abuse and food intake. However, a role for orexin in sexual reward has yet to be investigated. Orexin neurons are activated by sexual behavior, but endogenous orexin does not appear to be essential for sexual performance and motivation in male rats. Therefore, the goal of the current study was to test the hypothesis that orexin is critically involved in processing of sexual reward in male rats. First, it was demonstrated following exposure to conditioned contextual cues associated with sexual behavior in a conditioned place preference paradigm that cFos expression is induced in orexin neurons, indicating activation of orexin neurons by cues predicting sexual reward. Next, orexin-cell specific lesions were utilized to determine the functional role of orexin in sexual reward processing. Hypothalami of adult male rats were infused with orexin-B-conjugated saporin, resulting in greater than 80% loss of orexin neurons in the perifornical-dorsomedial and lateral hypothalamus. Orexin lesions did not affect expression of sexual behavior, but prevented formation of conditioned place preference for a sexual behavior paired chamber. In contrast, intact sham-treated males or males with partial lesions developed a conditioned place preference for mating. Orexin lesioned males maintained the ability to form a conditioned place aversion to lithium chloride-induced visceral illness, indicating that orexin lesions did not disrupt associative contextual memory. Overall, these findings suggest that orexin is not essential for sexual performance or motivation, but is critical for reward processing and conditioned cue-induced seeking of sexual behavior.  相似文献   

2.
Female rats express a conditioned place preference (CPP) for a context paired with mating. During a mating encounter, the female rat is exposed to several different types of stimuli, including, but not limited to, vaginocervical stimulation and social contact. The present experiment tested the hypothesis that two components of the mating interaction, vaginocervical stimulation or social contact, each induce a CPP in female rats. During conditioning rats received nonpaced mating, artificial vaginocervical stimulation, social interaction or a control treatment. Rats expressed a CPP for the context paired with nonpaced mating or artificial vaginocervical stimulation whereas social interaction and the control treatment did not induce a CPP. The present findings highlight the important role that vaginocervical stimulation plays in the reinforcing effects of mating in female rats.  相似文献   

3.
Sexual behavior is a natural reward for many rodent species, and it often includes chemosensory-directed components. Chemosensory stimuli themselves may also be rewarding. Conditioned place preference (CPP) is one paradigm frequently used to test the rewarding properties of a range of stimuli. Males and females of several rodent species show a CPP for sexual behavior; however, it is currently unknown whether sexual behavior can induce a CPP in male Syrian hamsters. As male Syrian hamsters are an animal model commonly used for investigation of the neurobiology of sexual behavior, understanding the rewarding components of sexual stimuli will better direct future research on brain regions and neurotransmitters involved in these behaviors. Experiment 1 tested the prediction that male hamsters show a CPP for sexual behavior. Female chemosensory stimuli are essential for the display of sexual behavior in male hamsters; however, the rewarding properties of female chemosensory stimuli contained in vaginal secretions (VS) are uncertain. Therefore, experiment 2 tested the prediction that male hamsters show a CPP for VS. This study is the first demonstration that both sexual behavior and VS induce a CPP in male hamsters. Thus, female chemosensory stimuli are a natural reward in a species that is dependent on these stimuli for reproductive fitness.  相似文献   

4.
One way to evaluate sexual arousal is by measuring approach behavior to sexual incentive stimuli. In our case we measure approach behavior to an originally non-preferred compartment which is associated with the physiological state induced by mating. This change of preference indicative of a positive affective (reward) state can be evaluated by conditioned place preference (CPP). We have shown that the CPP induced by paced mating is mediated by opioids. The administration of opioids also induces a reward state. The present study was designed to compare the rewarding properties of paced mating and a morphine injection. One group of females was allowed to pace the sexual interaction before being placed in the non-preferred compartment. In alternate sessions they received a morphine injection before being placed in the preferred compartment. In another group of females, the treatments were reversed. Only the females placed in the originally non-preferred compartment after paced mating changed their original preference, suggesting that paced mating induces a positive affective, reward, state of higher intensity than a morphine injection of 1 mg/kg. In a second experiment we determined if females allowed to pace the sexual interaction for 1 h would still developed CPP. No change in preference was observed in the females that mated for 1 h without pacing the sexual interaction. On the other hand, females that received between 10 and 15 paced intromissions as well as females that paced the sexual interaction for 1 h developed a clear CPP. The second experiment demonstrated that pacing is rewarding even in an extended mating session in which the females received around 25 intromissions and several ejaculations. These results further demonstrate the biological relevance associated with the ability of the female to space coital stimulation received during mating. This positive affective state will contribute to increase sexual arousal the next time a rat finds an appropriate mate.  相似文献   

5.
Female rats engage in approach and avoidance behaviors directed toward the male to "pace" the rate of copulation. These pacing behaviors result in a pattern of vaginocervical stimulation that triggers a neuroendocrine reflex that is important for pregnancy to result from insemination. Each female rat has a preferred pacing interval, and females develop conditioned place preferences for paced sex versus nonpaced sex. Research from this laboratory has reported that extracellular dopamine concentrations in striatum and nucleus accumbens are greater in female rats that are engaging in paced sex compared with those engaging in nonpaced sex. Furthermore, females who have males removed at their preferred intervals during a copulatory bout show extracellular dopamine concentrations comparable to females engaging in paced sex. It is unclear, however, whether they would also develop a conditioned place preference for sex under such conditions. This experiment was designed to address this question. Female rats had six exposures each to a chamber in which they engaged in nonpaced sex and a chamber in which they engaged in paced or preferred pacing interval sex. Following conditioning trials, females were tested for a conditioned place preference. The findings indicate that female rats develop conditioned place preferences for paced sex and for sex in which the male is removed at her preferred interval. This suggests that sexual behavior is reinforcing to female rats when their preferred interval is achieved, whether or not they are actively controlling the rate of copulation.  相似文献   

6.
Association between the reward caused by consuming drugs and the context in which they are consumed is essential in the formation of morphine-induced conditioned place preference (CPP). Glucocorticoid receptor (GRs) activation in different regions of the brain affects reward-based reinforcement and memory processing. A wide array of studies have demonstrated that blockage of GRs in some brain areas can have an effect on reward-related memory; however, to date there have been no systematic studies about the involvement of glucocorticoids (GCs) in morphine-related reward memory. Here, we used the GR antagonist RU38486 to investigate how GRs blockage affects the sensitization and CPP behavior during different phases of reward memory included acquisition, retrieval and reconsolidation. Interestingly, our results showed RU38486 has the ability to impair the acquisition, retrieval and reconsolidation of reward-based memory in CPP and sensitization behavior. But RU38486 by itself cannot induce CPP or conditioned place aversion (CPA) behavior. Our data provide a much more complete picture of the potential effects that glucocorticoids have on the reward memory of different phases and inhibit the sensitization behavior.  相似文献   

7.
Two experiments assessed the effects of neonatal testosterone treatment on paced mating behavior and conditioned place preference in female rats. In both experiments, females received s.c. injections of 5.0 microg testosterone propionate or oil vehicle at three days postpartum. As adults, females were ovariectomized and given s.c. injections of 10 microg estradiol benzoate and 500 microg progesterone, 48 and 4 h before mating, respectively. In Experiment 1, TP- and Oil-treated females exhibited similar high levels of lordosis responsiveness, but TP-treated females showed increased intervals between mounts and between intromissions in paced and non-paced mating conditions compared to control females. The effect was particularly pronounced during paced mating, when contact return latencies were increased approximately 2-fold by TP treatment. TP-treated females showed exaggerated pacing behavior, showing significantly greater return latencies after intromissions than Oil-treated females. In Experiment 2, TP- and Oil-treated groups were tested in a conditioned place preference paradigm to determine if the behavioral changes observed in Experiment 1 were in part a result of changes in the perceived reward produced by paced mating. TP treated and control females developed equivalent preferences for places associated with paced but not non-paced mating, indicating that neonatal TP treatment at this dosage does not disrupt or enhance the conditioned place preference induced by paced mating. The results of the two experiments demonstrate that neonatal TP treatment alters the display of pacing behavior but not the reward state induced by paced mating, and suggest that TP affects neural substrates involved in performance of paced mating without effects on those controlling lordosis or place preference conditioning.  相似文献   

8.

Background

MicroRNA (miRNA) emerges as important player in drug abuse. Yet, their expression profile in neurological disorder of cocaine abuse has not been well characterized. Here, we explored the changes of miRNA expression in rat hippocampus following repeated cocaine exposure and subsequent abstinence from cocaine treatment.

Results

Conditioned place preference (CPP) procedure was used to assess the acquisition and extinction of cocaine-seeking behavior in rats. MiRNA microarray was performed to examine miRNAs levels in rat hippocampus. Quantitative RT-PCR was conducted to further confirm results in microarray study. Finally, bioinformatic predictions were made to suggest potential target genes of cocaine-responsive miRNA in this study. MiRNA array found that 34 miRNA levels were changed in rat hippocampus while acquiring cocaine CPP and 42 miRNAs levels were altered after the cocaine-induced CPP were extinguished, as compared to normal controls. The findings from qRT-PCR study support results from microarray analysis.

Conclusions

The current study demonstrated dynamic changes in miRNA expression in rat hippocampus during the acquisition and extinction of cocaine-induced CPP. Some miRNAs which have been previously reported to be involved in brain disorders and drug abuse, including miR-133b, miR-134, miR-181c, miR-191, miR-22, miR-26b, miR-382, miR-409-3p and miR-504, were found to be changed in their expression following repeated cocaine exposure and subsequent abstinence from cocaine treatment. These findings may extend our understanding of the regulatory network underlying cocaine abuse and may provide new targets for the future treatment of drug abuse.  相似文献   

9.
The present experiments were conducted to explore the nature of conditioned sexual proceptivity in female quail. Females exposed to males subsequently approached the area where the males were previously housed (Experiment 1). This increased preference for the male's area reflected an increase in female sexual proceptivity and not an increase in non-directed locomotor activity (Experiment 2). These findings provide the first evidence that female quail show conditioned responses that may be considered to be proceptive responses toward male conspecifics. The proceptive responses are expressed as tonic changes in preference for areas where males have been observed in the past rather than as specific phasic conditioned responses.  相似文献   

10.
个体间的社会互作是一种天然奖赏,这种社会性奖赏诱导的条件位置偏爱(Conditioned place preference,CPP)是通过环境信息和社会互作奖赏效应间建立条件反射形成的,与药物奖赏诱导的CPP相似。棕色田鼠(Microtus mandarinus)是一种社会性单配制田鼠,具有紧密的亲-子联系和社会互作;雄鼠对断乳前幼仔也提供较高水平的亲本抚育。幼仔强化能够诱导母鼠及父鼠形成CPP,但双亲对幼仔是否也具有强化效应还不清楚。为探讨断乳前幼仔与双亲形成的奖赏联系,本实验检测了出生后13-17 d和19-23 d两个发育龄段的棕色田鼠幼仔对母鼠、父鼠以及可卡因(20 mg/kg)的CPP反应。数据显示在分别用母鼠、父鼠或可卡因强化后,两个年龄段的幼仔在CPP箱的强化室与非强化室所处时间没有显著性差异。这些结果表明断乳前棕色田鼠幼仔不能形成对母鼠、父鼠及可卡因的位置偏爱。  相似文献   

11.

Objective

To study the effect of rhynchophylline on N-methyl d-aspartate receptor subtype 2B subunit in hippocampus of Methamphetamine-induced conditioned place preference (CPP) mice.

Methods

Place preference mice models were established by methamphetamine; the expression of NR2B was observed by immunohistochemistry technique and Western blot.

Results

Methamphetamine (4 mg/kg)-induced place preference mice model was successfully established; ketamine (15 mg/kg), rhynchophylline (40 mg/kg) and rhynchophylline (80 mg/kg) can eliminate place preference; Immunohistochemistry showed that the number of NR2B-positive neurons in hippocampus was increased in the methamphetamine model group, whereas less NR2B-positive neurons were found in the ketamine group, low and high dosage rhynchophylline group. Western blot showed that the expression of NR2B protein was significantly increased in the model group, whereas less expression was found in the ketamine group, low and high dosage rhynchophylline group.

Conclusions

NR2B plays an important role in the formation of methamphetamine-induced place preference in mice. Rhynchophylline reversed the expression of NR2B in the hippocampus demonstrates the potential effect of mediates methamphetamine induced rewarding effect.  相似文献   

12.
The ability to control or pace the sexual interaction has important physiological and behavioral consequences for the female rat. Paced mating favors reproduction and induces a positive affective state as revealed by conditioned place preference (CPP). In the present experiment we evaluated: 1) If paced mating induces CPP in naturally cycling females; 2) If females developed a positive affective state if they paced the sexual interaction through a 1- or a 3-hole pacing chamber; 3) If females that mate with the same male without pacing the sexual interaction develop CPP. In the first experiment intact females were divided in 4 different groups; 2 paced the sexual interaction until receiving 1 or 3 ejaculations; the other 2 groups mated, without pacing the sexual interaction, until receiving 1 or 3 ejaculations. Only the group that paced the sexual interaction until receiving 3 ejaculations developed a positive affective state. In experiments 2 and 3 hormonally treated ovariectomized females were used. In experiment 2 females were allowed to pace the sexual interaction through a 1- or a 3-hole pacing chamber: A clear positive affective state was induced in both testing conditions. Finally, in experiment 3 females did not develop CPP for non-paced sex despite the fact that they mated with the same male in the conditioning sessions. These results demonstrate that the pattern of vaginocervical stimulation that the females received by engaging in approach and avoidance behaviors to pace the sexual interaction can induce a positive affective state in naturally cycling females. They also confirm the existence of a threshold of vaginocervical stimulation for paced mating to induce CPP in female rats.  相似文献   

13.
Many data indicate that endogenous opioid system is involved in amphetamine-induced behavior. Neuropeptide FF (NPFF) possesses opioid-modulating properties. The aim of the present study was to determine whether pharmacological modulation of NPFF receptors modify the expression of amphetamine-induced conditioned place preference (CPP) and amphetamine withdrawal anxiety-like behavior, both processes relevant to drug addiction/abuse. Intracerebroventricular (i.c.v.) injection of NPFF (5, 10, and 20 nmol) inhibited the expression of amphetamine CPP at the doses of 10 and 20 nmol. RF9, the NPFF receptors antagonist, reversed inhibitory effect of NPFF (20 nmol, i.c.v.) at the doses of 10 and 20 nmol and did not show any effect in amphetamine- and saline conditioned rats. Anxiety-like effect of amphetamine withdrawal was measured 24h after the last (14 days) amphetamine (2.5mg/kg, i.p.) treatment in the elevated plus-maze test. Amphetamine withdrawal decreased the percent of time spent by rats in the open arms and the percent of open arms entries. RF9 (5, 10, and 20 nmol, i.c.v.) significantly reversed these anxiety-like effects of amphetamine withdrawal and elevated the percent of time spent by rats in open arms at doses of 5 and 10 nmol, and the percent of open arms entries in all doses used. NPFF (20 nmol) pretreatment inhibited the effect of RF9 (10 nmol). Our results indicated that stimulation or inhibition of NPFF receptors decrease the expression of amphetamine CPP and amphetamine withdrawal anxiety, respectively. These findings may have implications for a better understanding of the processes involved in amphetamine dependence.  相似文献   

14.
The endogenous brain opioid system is believed to play an important role in mediating reward mechanisms. Opioid innervation is high in many limbic regions and reinforcing actions of many drugs of abuse, including cocaine, are thought to be mediated via endogenous opioid system. The aim of the present study was to indicate whether the anti-opioid peptide, neuropeptide FF (NPFF; FLFQPQRF-NH2) was able to modify the rewarding effect of cocaine (5 mg/kg) measured in the expression of conditioned place preference (CPP) test in rats and the expression of sensitization to hyperlocomotor effect of cocaine (10 mg/kg) in mice. Our results indicate that NPFF (5, 10, and 20 nmol) given intracerebroventricularly (i.c.v.) inhibited the expression of cocaine-induced CPP at the dose of 10 nmol (P < 0.01) and 20 nmol (P < 0.001). Moreover, NPFF inhibited the expression of cocaine-induced sensitization to its hyperlocomotor effect at the dose of 20 nmol (P < 0.05) and acute hyperlocomotor effect of cocaine at doses of 5 nmol (P < 0.01), 10 nmol (P < 0.01), and 20 nmol (P < 0.05). Our study suggests that NPFF may participate in a rewarding effect of cocaine measured in the CPP paradigm. On the other hand, our experiments indicate that NPFF is involved in the mechanism of expression of sensitization to cocaine hyperlocomotion but this effect seems to be non-specific because NPFF also inhibited the acute hyperlocomotor effect of cocaine.  相似文献   

15.
It is well established that male rat reproductive behaviors including sexual arousal, motivation, and performance are dependent on circulating levels of testosterone (T). The present study was designed to (1) compare the relative amount of T required to restore these different aspects of behavior in castrated rats, and (2) create an animal model for clinical populations with sexual impairments. Twenty-nine male Long–Evans rats were tested before and after castration for sexual performance (copulation), motivation (partner preference), and arousal (50 kHz ultrasonic vocalizations; measured together with scent marking). Sexual arousal was also inferred from copulation data. Rats were then assigned to one of four groups, and T was re-introduced via Silastic capsule implants varying in length and content: No T (empty capsules), Low T (2 mm capsules), Medium T (5 mm capsules), or High T (two 10 mm capsules). The highest dose was intended to restore physiological levels. Results indicate that High T is required for 50 kHz vocalizations, while Medium T was sufficient for the restoration of copulation, partner preference, and scent marking. These data suggest that sexual arousal may be most sensitive to reductions in testosterone. The role of T levels in measures of generalized and specific (sexual) arousal is discussed in the context of other reproductive behaviors. Furthermore, because the Low T group showed impairments across all behaviors during post-implant tests, we propose that these animals may provide a good animal model for studying clinical conditions marked by reduced motivation and arousal, including Hypoactive Sexual Desire Disorder.  相似文献   

16.
The hypothalamic neuropeptide orexin mediates arousal, sleep, and naturally rewarding behaviors, including food intake. Male sexual behavior is altered by orexin receptor-1 agonists or antagonists, suggesting a role for orexin-A in this naturally rewarding behavior. However, the specific role of endogenous orexin-A or B in different elements of male sexual behavior is currently unclear. Therefore, the current studies utilized markers for neural activation and orexin cell-specific lesions to test the hypothesis that orexin is critical for sexual motivation and performance in male rats. First, cFos expression in orexin neurons was demonstrated following presentation of a receptive or non-receptive female without further activation by different elements of mating. Next, the functional role of orexin was tested utilizing orexin-B conjugated saporin, resulting in orexin cell body lesions in the hypothalamus. Lesions were conducted in sexually naive males and subsequent sexual behavior was recorded during four mating trials. Lesion males showed shortened latencies to mount and intromit during the first, but not subsequent mating trials, suggesting lesions facilitated initiation of sexual behavior in sexually naive, but not experienced males. Likewise, lesions did not affect sexual motivation in experienced males, determined by runway tests. Finally, elevated plus maze tests demonstrated reduced anxiety-like behaviors in lesioned males, supporting a role for orexin in anxiety associated with initial exposure to the female in naive animals. Overall, these findings show that orexin is not critical for male sexual performance or motivation, but may play a role in arousal and anxiety related to sexual behavior in naive animals.  相似文献   

17.
It has been shown that orexin A in the ventral tegmental area (VTA) is necessary for development of morphine place preference. Additionally, D1 and D2 dopamine receptors in the nucleus accumbens (NAc) have critical roles in motivation and reward. However, little is known about the function of orexin in conditioned place preference (CPP) in rats and involvement of D1/D2 receptors in the NAc. In the present study, we investigated the effect of direct administration of orexin A into the VTA, and examined the role of intra-accumbal dopamine receptors in development (acquisition) of reward-related behaviors in the rats. Adult male Wistar rats were unilaterally implanted by two separate cannulae into the VTA and NAc. The CPP paradigm was used, and, conditioning score and locomotor activity were recorded by Ethovision software. The results showed that unilateral intra-VTA administration of orexin A (27, 53 and 107ng/0.3μl saline) during conditioning phase induced CPP in a dose-dependent manner. The most effective dose of intra-VTA orexin-A in eliciting CPP was 107ng. However, intra-NAc administration of SCH 23390 (0.25, 1 and 4μg/0.5μl saline), a D1 receptor antagonist, and sulpiride (0.25, 1 and 4μg/0.5μl DMSO), a D2 receptor antagonist, inhibited the development of orexin-induced CPP. The inhibitory effect of D2 but not D1 receptor antagonist was exerted in a dose-dependent manner. It is supposed that the activation of VTA dopaminergic neuron by orexin impresses the D2 receptors more than D1 receptors in the NAc.  相似文献   

18.
In Experiment 1 castrated male rats were implanted with a Silastic capsule containing either E or cholesterol (CHOL) 35 days after castration. They were then tested for sexual incentive motivation and copulatory behaviors every 5th day for 3 weeks. None of the treatments affected sexual incentive motivation. After the last test, all subjects were implanted with DHT-containing Silastic capsules, and tests continued for another 3 weeks. While E + DHT enhanced sexual incentive motivation and copulatory behavior, DHT alone failed to do so. In Experiment 2 the aromatase inhibitor fadrozole (F) was combined with testosterone (T). T restored all behaviors to the level seen in intact rats, and F significantly reduced these effects. In fact, T + F was not different from DHT. T and DHT restored the weight of the prostate and seminal vesicles to levels close to those of intact rats. In Experiment 3 a lower dose of E was employed. Also this dose of E failed to affect sexual incentive motivation while E + DHT restored it to the level of intact animals. Castration enhanced the serum concentrations of LH and FSH. E alone caused a marked reduction, and E + DHT brought both gonadotropins back to the level of intact animals. It was concluded that the doses of E and DHT employed in these experiments were within or close to the physiological range, and that such doses of E completely fail to enhance sexual incentive motivation in castrated animals. DHT has small or no effects. It appears that sexual incentive motivation and copulation require simultaneous stimulation of androgen and estrogen receptors.  相似文献   

19.
Paced mating induces positive affect as revealed by conditioned place preference (CPP) in female rats. It has been suggested that endogenous opioids are involved in the generation of this positive affect since systemic administration of the opioid antagonist naloxone blocks mating-induced CPP. Several brain structures, including the medial preoptic area (mPOA), the ventromedial nucleus of the hypothalamus (VMH), the amygdala (Me), and the nucleus accumbens (Acb) have been implicated in the control of female sexual behavior. However, it is not known if these structures also participate in the positive affect produced by paced mating. To this end we determined the effects of intracranial administration of naloxone methiodide into the mPOA, VMH, Me and Acb on conditioned place preference induced by paced mating in female rats. Regardless of the site of infusion 5 μg of naloxone did not affect any of the sexual behavior parameters measured during copulation. When CPP was evaluated, the groups infused with naloxone into the mPOA, the VMH, and the Me before each conditioning session did not develop place preference. Only the group infused with naloxone in the Acb and the control groups did so. These results demonstrate that opioid receptors within the mPOA, VMH and Me are necessary for the rewarding aspects of paced mating. We suggest that the Me and VMH are important for the transmission of sensory information produced by copulation while the mPOA is the site where the positive affect is originated.  相似文献   

20.
A three-phase experiment manipulated sexual experience and hormone exposure (perinatally and in adulthood) in female rats housed individually from weaning so as to limit peripubertal social and sexual experience. Noncontact partner preference for a male or estrous female rat was measured both before and after sexual experience, first while rats were under the influence of circulating testosterone propionate (TP) and later after priming them with ovarian hormones (estradiol benzoate and progesterone; EB & P). When implanted with TP capsules and tested while sexually naive, all groups of female rats preferred females to males without differing statistically. However, following three sexual experience sessions with estrous females, differences emerged between the masculinized and control groups in the magnitude of their female-directed preference, with masculinized females demonstrating a significantly greater preference for estrous females. Sexual experience with male rats under EB & P did not result in a significant shift in preference in any group. Histological assessment indicated that the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) was increased by exposure to TP postnatally, and SDN-POA volume correlated positively with partner preference scores but only when rats were both sexually experienced and exposed to circulating TP in adulthood. These results suggest that sexual experience interacts with steroid exposure to shape partner preference.  相似文献   

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