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      An NMDA antagonist impairs copulation and the experience-induced enhancement of male sexual behavior in the rat.

      , ,
      Behavioral Neuroscience
      American Psychological Association (APA)

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          Abstract

          Sexual experience facilitates subsequent male sexual behavior; activation of the N-methyl-D-aspartate (NMDA) glutamate receptor may play a role in this experience-induced enhancement. In this article, the authors report that systemic injections of MK-801, an NMDA receptor antagonist, impaired male sexual behavior in sexually naive and sexually experienced male rats. Furthermore, saline-treated rats that received 7 daily exposures to an inaccessible estrous female instead of sexual experience displayed enhancement of copulation on the following day. Injections of MK-801 before each of these exposures inhibited the experience-induced enhancement on the drug-free test on Day 8. These data suggest that stimulation of NMDA receptors enhances sexual performance immediately and mediates the experience-induced enhancement of subsequent copulatory behavior.

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          Most cited references36

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          Synaptic plasticity and memory: an evaluation of the hypothesis.

          Changing the strength of connections between neurons is widely assumed to be the mechanism by which memory traces are encoded and stored in the central nervous system. In its most general form, the synaptic plasticity and memory hypothesis states that "activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation and is both necessary and sufficient for the information storage underlying the type of memory mediated by the brain area in which that plasticity is observed." We outline a set of criteria by which this hypothesis can be judged and describe a range of experimental strategies used to investigate it. We review both classical and newly discovered properties of synaptic plasticity and stress the importance of the neural architecture and synaptic learning rules of the network in which it is embedded. The greater part of the article focuses on types of memory mediated by the hippocampus, amygdala, and cortex. We conclude that a wealth of data supports the notion that synaptic plasticity is necessary for learning and memory, but that little data currently supports the notion of sufficiency.
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            Blocking of acquisition but not expression of conditioned fear-potentiated startle by NMDA antagonists in the amygdala.

            Receptors for N-methyl-D-aspartate (NMDA) seem to have a critical role in synaptic plasticity. NMDA antagonists (such as AP5) prevent induction of long-term potentiation, an activity-dependent enhancement of synaptic efficacy mediated by neural mechanisms that might also underlie learning and memory. They also attenuate memory formation in several behavioural tasks; there are few data, however, implicating an NMDA-sensitive measure of conditioning based on local infusion of antagonists into a brain area tightly coupled to the behavioural response used to assess conditioning. We now show that NMDA antagonists infused into the amygdala block the acquisition, but not the expression, of fear conditioning measured with a behavioural assay mediated by a defined neural circuit (fear-potentiation of the acoustic startle reflex). This effect showed anatomical and pharmacological specificity, and was not attributable to reduced salience of the stimuli of light or shock used in training. The data indicate that an NMDA-dependent process in the amygdala subserves associative fear conditioning.
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              Hormone-neurotransmitter interactions in the control of sexual behavior.

              The stimuli from a receptive female and/or copulation itself leads to the release of dopamine (DA) in at least three integrative hubs. The nigrostriatal system promotes somatomotor activity; the mesolimbic system subserves numerous types of motivation; and the medial preoptic area (MPOA) focuses the motivation onto specifically sexual targets, increases copulatory rate and efficiency, and coordinates genital reflexes. The previous (but not necessarily concurrent) presence of testosterone is permissive for DA release in the MPOA, both during basal conditions and in response to a female. One means by which testosterone may increase DA release is by upregulating nitric oxide synthase, which produces nitric oxide, which in turn increases DA release. Hormonal priming in females may also increase DA release in the MPOA, and copulatory activity may further increase DA levels in females. One of the intracellular effects of stimulation of DA D1 receptors in the MPOA of male rats may be increased expression of the immediate-early gene c-fos, which may mediate longer term responses to copulation. Furthermore, increased sexual experience led to increased immunoreactivity to Fos, the protein product of c-fos, following copulation to one ejaculation. Another intracellular mediator of DA's effects, particularly in castrates, may be the phosphorylation of steroid receptors. Finally, while DA is facilitative to copulation, 5-HT is generally inhibitory. 5-HT is released in the LHA, but not in the MPOA, at the time of ejaculation. Increasing 5-HT in the LHA by microinjection of a selective serotonin reuptake inhibitor (SSRI) increased the latency to begin copulating and also the latency to the first ejaculation, measured from the time the male first intromitted. These data may at least partially explain the decrease in libido and the anorgasmia of people taking SSRI antidepressants. One means by which LHA 5-HT decreases sexual motivation (i.e. increases the latency to begin copulating) may be by decreasing DA release in the NAcc, a major terminal of the mesolimbic system. Thus, reciprocal changes in DA and 5-HT release in different areas of the brain may promote copulation and sexual satiety, respectively.
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                Author and article information

                Journal
                Behavioral Neuroscience
                Behavioral Neuroscience
                American Psychological Association (APA)
                1939-0084
                0735-7044
                2003
                2003
                : 117
                : 1
                : 69-75
                Article
                10.1037/0735-7044.117.1.69
                12619909
                add91b42-8862-4f18-9f85-c83e1278662b
                © 2003
                History

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