Hypothalamic infusion of the 5-HT21C agonist, DOI, prevents the inhibitory actions of the 5-HT1A agonist, 8-OH-DPAT, on lordosis behavior

Behavioural Brain Research

2007

Ovariectomized rats with bilateral cannulae near the ventromedial nucleus of the hypothalamus were hormonally primed with 10μg estradiol benzoate and 500μg progesterone. Sexually receptive females were infused bilaterally with 200 ng of the 5-HT 1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), or with a combination of 200 ng 8-OH-DPAT and 2000 ng of the 5-HT 2 receptor agonist, (±)-2,5-dimethoxy-4-iodophenyl-2-aminopropane HCl (DOI). 8-OH-DPAT inhibited lordosis behavior and DOI reduced this inhibition. However, if females were preinfused with the PKC inhibitor, bisindolymaleimide I hydrochloride (BIM), DOI's effect was eliminated. BIM's attenuation of the effects of DOI was time-dependent. When BIM was infused 90 min, but not 30 min, before the 5-HT receptor agonists, BIM eliminated DOI's protection against the lordosisinhibiting effects of 8-OH-DPAT. A concentration of BIM as low as 10 −5 nmol in a 0.5μl infusion volume was effective and there was little evidence of dose responsivity between 10 −5 and 10 −1 nmol of BIM. In contrast, prior infusion with vehicle or with 10 −7 nmol BIM had no impact on the female's response to the 5-HT receptor agonists. These findings allow the suggestion that DOI's ability to increase PKC may be responsible for attenuation of the effects of 8-OH-DPAT on lordosis behavior. KeywordsPKC inhibitor; 5-HT 1A receptors; 5-HT 2 receptors; ovariectomized; sexual behavior IntroductionWithin the ventromedial nucleus of the hypothalamus (VMN), serotonin (5-HT) modulates female rat sexual behavior by acting on multiple 5-HT receptors [39]. Lordosis behavior, a supraspinal estrogen-dependent reflex of sexually receptive females [29], is inhibited by 5-HT 1A receptor agonists and facilitated by 5-HT 2 receptor agonists and their coactivation attenuates the lordosis-inhibitory effects of 5-HT 1A receptor agonists [39]. We have proposed that this 5-HT 1A /5-HT 2 receptor interaction enables the female to fine-tune her behavior so that it is most adaptive to environmental conditions [42]. However, the mechanisms for this interaction are not known.

Section: Introductionsupporting

confidence: 89%

Section: Surgical Procedures-whenmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

Selvamani

Lincoln

Behavioural Brain Research

2007

“…Activation of 5-HT 1A receptors in the ventromedial nucleus of the hypothalamus (VMN) are primarily responsible for the lordosis-inhibiting effects of 5-HT (Uphouse, et al, 1996; Uphouse and Caldarola-Pastuszka, 1993). In contrast, activation of 5-HT 2A/2C receptors facilitates the behavior (Gonzalez, et al, 1997; Wolf, et al, 1998) and attenuates lordosis inhibition mediated by 5-HT 1A receptors in the VMN (Uphouse, et al, 1994). Hormonal priming that facilitates lordosis behavior reduces functioning of 5-HT 1A receptors (Mize and Alper, 2000; Mize, et al, 2003) and enhances that of 5-HT 2A/2C receptors (Ansonoff and Etgen, 1998; Cyr, et al, 1998; Gorosito and Cambiasso, 2008; Karp, et al, 2007; Marino, et al, 2006; Sumner and Fink, 1995; Sumner and Fink, 1997).…”

Section: Introductionmentioning

confidence: 99%

Progesterone reduces the effect of the serotonin 1B/1D receptor antagonist, GR 127935, on lordosis behavior

Hiegel

Guptarak

et al. 2009

Hormones and Behavior

Ovariectomized rats were hormonally primed with 10 μg estradiol benzoate or with estradiol benzoate plus 500 μg progesterone. Rats received a bilateral infusion with 200 ng of the 5-HT 1B/1D receptor antagonist, N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)-1-1′-biphenyl-4-carboxamide hydrochloride (GR 127935), into the ventromedial nucleus of the hypothalamus (VMN), followed by a 5 min restraint or home cage experience. In estrogen-primed females that had experienced minimal handling between ovariectomy and use in the experiment, infusion with the water vehicle transiently inhibited lordosis behavior, and the 5-HT 1B/1D receptor antagonist amplified this inhibition. There were no effects in rats hormonally primed with estrogen and progesterone. Handling for two days before the experiment reduced the effects of the infusions in estrogen-primed rats. However, when a 5 min restraint experience followed infusion with GR 127935, there was a significant decline in lordosis behavior that persisted for 10 to 15 min after the experience. Regardless of the prior experience or type of infusion, the addition of progesterone to the hormonal priming completely prevented the lordosis inhibition. These findings are consistent with prior evidence that progesterone protects against the inhibitory effects of a 5 min restraint experience on lordosis behavior. Moreover, these are the first experiments to demonstrate an inhibitory effect of a selective 5-HT 1B/1D receptor antagonist in the VMN on lordosis behavior of estrogen primed, but not estrogen and progesterone primed, ovariectomized rats.

“…In contrast, agonists that act primarily on 5-HT 2 or 5-HT 3 receptors facilitate lordosis behavior in female rats with relatively low sexual receptivity (Mendelson and Gorzalka, 1985; Wolf et al, 1999; Wolf et al, 1998). A potentially beneficial effect of 5-HT 2 and 5-HT 3 receptors is inferred from observations that 5-HT 2 and 5-HT 3 receptor agonists protect against the lordosis-inhibiting effects of 5-HT 1A receptor agonists (Maswood et al, 1998; Uphouse et al, 1994) and that 5-HT 2 and 5-HT 3 receptor antagonists inhibit lordosis behavior (Gonzalez et al, 1997; Maswood et al, 1997). Therefore, drugs which lead to generalized increases in extracellular 5-HT could disrupt the balance between activation of 5-HT receptors that inhibit and those that facilitate lordosis behavior.…”

Section: 0 Introductionmentioning

confidence: 99%

Comparison of female Fischer and Sprague–Dawley rats in the response to ketanserin

Miryala

Hiegel

Pharmacology Biochemistry and Behavior

2013

The effects of the 5-HT2A/2C receptor antagonist, ketanserin, on lordosis behavior were examined in hormonally primed, ovariectomized Fischer and Sprague-Dawley females. Rats were primed with 0.067 μg/g body weight estradiol benzoate and 3.33 μg/g body weight progesterone. After a pretest for sexual behavior, rats were injected with 0.416 to 10 mg/kg ketanserin. In both strains, lordosis behavior, lordosis quality, and proceptivity were significantly reduced by ketanserin. There was modest evidence of a strain difference with Sprague-Dawley females slightly more sensitive to ketanserin. In a second experiment, the effects of 10 mg/kg fluoxetine, 1 mg/kg ketanserin, and their combination were examined to determine if the two drugs would have additive effects on sexual behavior. There was no evidence that the drugs were additive in their effect and the strains did not differ in their response to the combined treatment. These findings are discussed in relation to prior evidence for strain differences in the sexual behavioral response to fluoxetine and to a receptor agonist acting preferentially at 5-HT1A receptors.