The anti-aggressive drug eltoprazine preferentially binds to 5-HT1A and 5-HT1B receptor subtypes in rat brain: sensitivity to guanine nucleotides

Sijbesma, H.; Schipper, J.; Kloet, E. Ronald de

doi:10.1016/0014-2999(90)90008-t

Cited by 32 publications

(13 citation statements)

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“…As mentioned earlier, in a resident /intruder model, eltoprazine, the 5-HT 1 agonist, produces a dose-dependent decrease in offensive aggression in a rat resident /intruder model without altering other behaviors, including defensive aggression (Sijbesma et al, 1990). This unique pharmacological profile fits a class of drugs called "serenics" (Olivier and Mos, 1990).…”

Section: Discussionmentioning

confidence: 99%

“…For example, rats show an increase in offensive aggression after treatment with neurotoxins that deplete 5-HT levels in the hypothalamus (Vergnes et al, 1988). Conversely, rats treated with eltoprazine, a 5-HT 1 receptor agonist, show a dose-dependent decrease in offensive aggression (Sijbesma et al, 1990). Several studies have reported elevations in CNS levels of 5-HT after treatment with the selective 5-HT reuptake inhibitor fluoxetine (Guan and McBride, 1988;Auerbach et al, 1989;Perry and Fuller, 1992).…”

Section: Abstract: Fluoxetine; Vasopressin; Serotonin; Anterior Hypomentioning

confidence: 99%

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Vasopressin/Serotonin Interactions in the Anterior Hypothalamus Control Aggressive Behavior in Golden Hamsters

et al. 1997

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Studies in several species of rodents show that arginine vasopressin (AVP) acting through a V 1A receptor facilitates offensive aggression, i.e., the initiation of attacks and bites, whereas serotonin (5-HT) acting through a 5-HT 1B receptor inhibits aggressive responding. One area of the CNS that seems critical for the organization of aggressive behavior is the basolateral hypothalamus, particularly the anterior hypothalamic region. The present studies examine the neuroanatomical and neurochemical interaction between AVP and 5-HT at the level of the anterior hypothalamus (AH) in the control of offensive aggression in Syrian golden hamsters. First, specific V 1A and 5-HT 1B binding sites in the AH are shown by in vitro receptor autoradiography. The binding for each neurotransmitter colocalizes with a dense field of immunoreactive AVP and 5-HT fibers and putative terminals. Putative 5-HT synapses on AVP neurons in the area of the AH are identified by double-staining immunocytochemistry and laser scanning confocal microscopy. These morphological data predispose a functional interaction between AVP and 5-HT at the level of the AH. When tested for offensive aggression in a resident /intruder paradigm, resident hamsters treated with fluoxetine, a selective 5-HT reuptake inhibitor, have significantly longer latencies to bite and bite fewer times than vehicle-treated controls. Conversely, AVP microinjections into the AH significantly shorten the latency to bite and increase biting attacks. The action of microinjected AVP to increase offensive aggression is blocked by the pretreatment of hamsters with fluoxetine. These data suggest that 5-HT inhibits fighting, in part, by antagonizing the aggressionpromoting action of the AVP system. Two neurotransmitter systems implicated in the control of aggressive behavior are arginine vasopressin (AVP) and serotonin (5-HT). AVP is a neurochemical signal affecting numerous brain functions (DeWied, 1971;Cooper et al., 1979;Pittman et al., 1982;Fehm-Wolfsdorf et al., 1988;Dantzer and Bluthe, 1992), including aggression (Ferris and Potegal, 1988, Koolhaas et al., 1990Potegal and Ferris, 1990;Winslow et al., 1993; Delville et al., 1996a,b). For example, microinjection of AVP V 1A -receptor antagonist into the anterior hypothalamus (AH) of a hamster causes a dose-dependent inhibition of offensive aggression, i.e., initiated attacks and bites toward a conspecific placed into their home cage (Ferris and Potegal, 1988). Similarly, AVP receptor blockade in the AH significantly reduces aggression between hamsters paired together in a neutral arena .Although AVP facilitates offensive aggression, 5-HT is reported to have the opposite effect and diminishes aggressive behavior (for review, see Olivier and Mos, 1990). For example, rats show an increase in offensive aggression after treatment with neurotoxins that deplete 5-HT levels in the hypothalamus (Vergnes et al., 1988). Conversely, rats treated with eltoprazine, a 5-HT 1 receptor agonist, show a dose-dependent decrease in offensive aggressi...

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Section: Discussionmentioning

confidence: 99%

Section: Abstract: Fluoxetine; Vasopressin; Serotonin; Anterior Hypomentioning

confidence: 99%

Vasopressin/Serotonin Interactions in the Anterior Hypothalamus Control Aggressive Behavior in Golden Hamsters

et al. 1997

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“…This possibility is supported by the presence of 5-HT terminals on hypothalamic AVP neurons in golden hamsters (Ferris et al, 1997). Moreover, as the effects of 5-HT are presumed to involve 5-HT 1A / B receptors (Sijbesma et al, 1990(Sijbesma et al, , 1991Joppa et al, 1997), these colocalize with AVP receptors within the hypothalamus Ferris et al, 1997), (C. F. Ferris, unpublished results).…”

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confidence: 90%

Behavioral and Neurobiological Consequences of Social Subjugation during Puberty in Golden Hamsters

1998

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In golden hamsters, offensive aggression is facilitated by vasopressin and inhibited by serotonin. We tested whether these neurotransmitter systems respond to modifications resulting from the stress of threat and attack (i.e., social subjugation) during puberty. Male golden hamsters were weaned at postnatal day 25 (P25), exposed daily to aggressive adults from P28 to P42, and tested for offensive aggression as young adults (P45). The results showed a context-dependent alteration in aggressive behavior. Subjugated animals were more likely to attack younger and weaker intruders than nonsubjugated controls. Conversely, subjugated animals were less likely to attack animals of similar size and age. After testing, the animals were killed, and their brains were collected to determine whether these behavioral changes are underlined by changes in the vasopressin and serotonin systems. Social subjugation resulted in a 50% decrease in vasopressin levels within the anterior hypothalamus, a site involved in the regulation of aggression. Furthermore, whereas the density of vasopressin-immunoreactive fibers within the area was not significantly altered in subjugated animals, the number of serotonin-immunoreactive varicosities within the anterior hypothalamus and lateral septum was 20% higher in subjugated animals than in their controls. These results establish puberty as a developmental period sensitive to environmental stressors. Furthermore, the results show that changes in the vasopressin and serotonin systems can correlate with behavioral alterations, supporting the role of these two neurotransmitters in the regulation of aggression.

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“…The 5‐HT1B receptor is located both presynaptically (where it is believed to control serotonin release) and postysnaptically 77 . The antiaggressive effects of 5‐HTIB are believed to be mediated by the postsynaptic receptor, 78,79 inasmuch as lesioning the central serotonergic system does not alter the antiaggressive properties of serenics. These animal studies have important implications for the neurobiology of suicide, inasmuch as impulsive behavior in humans (including violent suicide) has been associated with a decrease in central serotonergic activity could result in a decreased activation of the postsynaptic 5‐HT1B receptor, which may result in aggressive and/or impulsive behavior.…”

Section: Serotonin 1b Receptors Serotonin 2a Receptors Corticosteromentioning

confidence: 99%

Regulation of 5‐HT Receptors and the Hypothalamic‐Pituitary‐Adrenal Axis

López

Vázquez

Chalmers

et al. 1997

Annals of the New York Academy of Sciences

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Disturbances in the serotonin (5-HT) system is the neurobiological abnormality most consistently associated with suicide. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is also described in suicide victims. The HPA axis is the classical neuroendocrine system that responds to stress and whose final product, corticosteroids, targets components of the limbic system, particularly the hippocampus. We will review results from animal studies that point to the possibility that many of the 5-HT receptor changes observed in suicide brains may be a result of, or may be worsened by, the HPA overactivity that may be present in some suicide victims. The results of these studies can be summarized as follows: (1) chronic unpredictable stress produces high corticosteroid levels in rats; (2) chronic stress also results in changes in specific 5-HT receptors (increases in cortical 5-HT2A and decreases in hipocampal 5-HT1A and 5-HT1B); (3) chronic antidepressant administration prevents many of the 5-HT receptor changes observed after stress; and (4) chronic antidepressant administration reverses the overactivity of the HPA axis. If indeed 5-HT receptors have a partial role in controlling affective states, then their modulation by corticosteroids provides a potential mechanism by which these hormones may regulate mood. These data may also provide a biological understanding of how stressful events may increase the risk for suicide in vulnerable individuals and may help us elucidate the neurobiological underpinnings of treatment resistance.

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The anti-aggressive drug eltoprazine preferentially binds to 5-HT1A and 5-HT1B receptor subtypes in rat brain: sensitivity to guanine nucleotides

Cited by 32 publications

References 54 publications

Vasopressin/Serotonin Interactions in the Anterior Hypothalamus Control Aggressive Behavior in Golden Hamsters

Vasopressin/Serotonin Interactions in the Anterior Hypothalamus Control Aggressive Behavior in Golden Hamsters

Behavioral and Neurobiological Consequences of Social Subjugation during Puberty in Golden Hamsters

Regulation of 5‐HT Receptors and the Hypothalamic‐Pituitary‐Adrenal Axis

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