Jorge F. Rodriguez-Sierra

Analgesic effect of vaginal stimulation in rats: Modulation by graded stimulus intensity and hormones ☆

Abstract Stimulation of the vaginal cervix with a glass rod elevated vocalization thresholds to tail shock in ovariectomized rats. As more force (in g) was applied to the cervix, we observed a progressive increase in the threshold of vocalization in response to tail shock. In a second experiment, ovariectomized rats were treated with either estradiol benzoate, progesterone, estradiol plus progesterone, or oil, and tested for vocalization to tail shock. Estradiol treatment enhanced the effect of cervical stimulation on elevating the vocalization threshold. Progesterone had no such effect when given alone, but completely prevented the estrogen effect. These findings demonstrate that a) vocalization in response to noxious stimulation is suppressed by genital tract stimulation, b) the degree of suppression increases with increasing intensity of genital tract stimulation, and c) steroid hormones affect this phenomenon.

Analgesia induced by vaginal stimulation in rats is apparently independent of a morphine-sensitive process

Previous studies have suggested that in rats probing against the vaginal cervix with a glass rod is analgesic, for this stimulus elevates the threshold for eliciting vocalization in response to tail shock. In the present studies pretreatment with naloxone HCl (1 or 10 mg/kg), a potent narcotic antagonist, did not antagonize this vaginal stimulation-induced analgesia. Furthermore, vaginal stimulation was found to exert its analgesic effect even in rats made tolerant to, and dependent upon, morphine sulfate. These results suggest that the analgesic effect of vaginal stimulation is not necessarity mediated by an opiatesensitive neural system. However, we hypothesize that even though vaginal stimulation and other analgesic manipulations may act via different neural substrates, they may nevertheless converge onto a final common mechanism for pain suppression.

Monoaminergic mediation of the antinociceptive effect of vaginal stimulation in rats.

Abstract In rats, probing against the vaginal cervix with a glass rod elevated the current threshold required to elicit vocalization in response to tail shock. This elevation in vocalization threshold was significantly attenuated by depletion of norepinephrine (NE) with synthesis inhibitors, blockade of alpha-NE receptors, and systemic or central administration of 6-hydroxydopamine. Furthermore, NE receptor stimulation significantly increased vocalization thresholds prior to and during vaginal stimulation. In contrast, dopamine (DA) receptor stimulation reduced, while DA receptor blockade enhanced, this antinociceptive effect of vaginal stimulation. Similarly, serotonin (5-HT) receptor stimulation reduced, and 5-HT depletion enhanced, this antinociceptive effect. Vaginal stimulation also induced an elevation in current threshold for leg withdrawal in response to foot shock. However, this threshold was completely unaffected by the monoamine synthesis inhibitors. In rats pretreated with a catecholamine synthesis inhibitor, two minutes of vaginal stimulation further reduced NE levels in the spinal cord, but did not affect telencephalon, hypothalamus, thalamus or midbrain. In addition, vaginal stimulation inpeded the depletion of striatal DA, with no effect on telencephalic DA. These findings suggest that vaginal stimulation activates NE neurons and decreases activity in DA neurons. At least part of this apparently analgesic effect of genital tract stimulation may be mediated by supraspinal monoaminergic mechanisms, some of which have a descending component that inhibits transmission in spinal pain pathways.

Effects of prostaglandin E2 and indomethacin on sexual behavior in the female rat

Abstract Prostaglandin E2 (PGE2) facilitated sexual behavior in estrogen-primed ovariectomized or ovariectomized-adrenalectomized rats. Administration of indomethacin, an inhibitor of prostaglandin synthesis, attenuated the effectiveness of estrogen and progesterone in inducing sexual receptivity in ovariectomized rats. Concurrent administration of PGE2 with indomethacin restored sexual behavior only when administered early in the estrogen-priming period but not if administered along with the progesterone. Our studies support the likelihood of a role of prostaglandins in the control of sexual behavior in the female rat.

Lordosis: Inhibiting effects of progesterone in the female rat

The effectiveness of progesterone (P) in inhibiting sexual behavior in the rat was tested. 2 doses of P were used .5 and 5.0 mg. In the 1st experiment, ovariectomized rats were given either dose of P 1 hour before receiving a 5 mcg/kg dose of estradiol benzoate (EB). 44 hours later sexual behavior was tested. .5 mg P was then given and sexual behavior retested. 5 mg prior to the start of estrogen conditioning inhibited the facilitatory effects on lordosis of a 2nd injection of P 44 hours after EB. This was exhibited only for the high dosage. In a 2nd experiment, ovariectomized rats received 5 mcg EB and were pretested for sexual behavior 44 hours later. Animals then received P at 1 of 2 doses and were tested for sexual behavior 4 hours later. After 20 hours, sexual behavior was again tested; animals received .5 mg P and were retested. Both the high and low dose facilitated lordosis 44 hours after EB. 4 hours after the 2nd injection both groups were inhibited. Finally, ovariectomized rats were pretested for sexual behavior as in the 2nd experiment and injected with 5 mg of P, tested for sexual behavior 4 hours later, and retested 20 hours after that. Animals then either received a control injection or .5 mg P and tested 4 hours later. Animals were facilitated by the high dose. However, the 2nd dose depressed sexual activity. Results in the first 2 experiments indicate that the rat has 2 types of inhibitory actions on sexual behavior. The dose required to produce sequential inhibition in rats is lower than the dose required to produce concurrent inhibition.

Monoaminergic mediation of masculine and feminine copulatory behavior in female rats.

Ovariectomized rats treated with testosterone propionate (TP; 100 mug/kg X 6 days) and para-chlorophenylalanine (pCPA; 100 mg/kg X 3 days), a serotonin synthesis inhibitor, showed more masculine copulatory behavior (including the ejaculatory pattern) than did females receiving either TP or pCPA alone. The facilitatory effect of pCPA on the masculine copulatory behavior in females was not potentiated by pargyline (50 or 100 mg/kg), a monoamine oxidase inhibitor; instead, pargyline antagonized the effect of pCPA. Apomorphine (100 mug/kg), a dopamine receptor stimulant, did not increase masculine copulatory behavior in TP treated females. Adopaminergic facilitatory effect was therefore not demonstrated. These results suggest a serotonin-mediated inhibition of masculine copulatory behavior in female rats. When feminine copulatory behavior was tested, females receiving TP plus pCPA plus pargyline, TP plus pargyline, or TP plus apomorphine displayed lordosis in response to mounting by male rats. Lordosis did not occur after administration of TP, PCPA, or pargyline, individually or in any other combination. The responses in pargyline groups are consistent with the hypothesis of a noradrenergic facilitatory system for lordotic behavior. The responses in the apomorphine group are discussed in terms of a possible role for low level dopaminergic stimulation in facilitating lordosis.

Does prolactin play a role in estrogen-induced maternal behavior in rats: apomorphine reduction of prolactin release.

40 pregnant rats, ovariectomized and hysterectomized on Day 16 of pregnancy were treated with estradiol benzoate (EB) to stimulate maternal behavior and apomorphic hydrochloride (APO) to block prolactin (PRL) release in order to investigate the role of PRL in EB-induced maternal behavior. EB was administered immediately after surgery and APO was given in doses of 5 mg/kg 4-6 hours before surgery and 18, 30, and 42 hours after surgery. Maternal behavior was tested with the presence of pups 48 hours after treatment. Behavior patterns looked for included retrieval and nursing posture. The median latencies for the onset of maternal behavior were significantly different among the 4 groups: EB-treated (Group 1), EB + APO (Group 2), oil (Group 3), and oil + APO (Group 4) (p less than .2). Groups 1 and 2 had significant shorter latencies than corresponding controls: Group 1 vs. 3 and Group 2 vs. 4 (p less than .05 and less than .01, respectively) 90% of females in Groups 1 and 2 exhibited maternal behavior after 24 hours of exposure to pups. These results indicate that increased PRL secretion is unnecessary for estrogen-induced maternal behavior.

Hypophysectomy Facilitates Sexual Behavior in Female Rats

Lordosis was elecited in 49% of 87 hormonally untreated, hypophysectomized-ovariectomized (hypox-ovx) female rats in response to palpation of the flanks and perineum (vaginal stimulation was not applied). By contrast, only 12% of 113 hormonally untreated ovariectomized (ovx) rats showed lordosis in response to such stimulation. Subsequently, hypox-ovx and ovx-only rats were given daily injections of 1 mug/kg estradiol benzoate (EB) and tested for sexual receptivity with males. Teh estrogen-treated hypox-ovx females became sexually receptive significantly earlier, and exhibited higher lordosis quotients and more soliciting behavior, than the estrogen-treated ovx-only rats. The increased sexual responsiveness in the hypox-ovx rats could be due to increased LRH activity. To test this, we treated hypox-ovx rats with dihydrotestosterone propionate (DHT-P), which suppresses plasma LH levels but is relatively ineffective in inducing sexual receptivity, and found a significant depression of lordosis responsiveness. These experiments suggest that hypox-ovx females show a heightened responsiveness to hormonal and/or sensory factors that induce a lordosis response, possibly because of increased LRH activity.

Intrahypothalamic Implants of Progesterone Inhibit Lordosis Behavior in Ovariectomized, Estrogen-Treated Rats

Intracranial implants of crystalline progesterone (P) were used to examine in site of action of Ps facilitatory and inhibitory effects on lordosis behavior in the ovariectomized, estradiol-benzoate (EB)-primed RAT. P implanted in the medial basal hypothalamus (MBH) 1 h prior to subcutaneous (s.c.) EB injection inhibited lordosis in response to a systemic P injection 44 h after EB (concurrent inhibition). P implanted in the MBH did not facilitate lordosis when implanted 44 h after EB injection, but this same implant of P inhibited lordosis in response to P injection 68 h after EB (sequential inhibition). Cholesterol (Chol) implants in the MBH did not inhibit lordosis behavior in either the concurrent or the sequential inhibition experimental paradigms. The results indicate that the MBH is an important site of P inhibition of sexual receptivity in the rat.

Induction of lordosis responsiveness by vaginal stimulation in rats is independent of anterior or posterior pituitary hormones

Abstract In a previous study, rats that initially did not show lordosis in response to palpation of the flanks and perineum started to show lordosis to this stimulus when tested 10 sec after brief vaginal stimulation and continued to show lordosis responsiveness for more than 3 hr. In the present study, we tested the possibility that this effect of vaginal stimulation is mediated by the release of pituitary hormones. Hypophysectomized rats showed the lordosis-activating effect of vaginal stimulation, and this effect persisted for more than 1 hr, similar to rats with intact pituitaries. Oxytocin (50 or 100 mU/rat) or vasopressin (100 mU/rat) injected systemically did not induce lordosis responding in ovariectomized rats that received either a single injection of estradiol benzoate (2 μg/Kg) or no hormonal treatment. However, these individuals subsequently showed the lordosis-activating effect of vaginal stimulation. The mechanism by which vaginal stimulation activates lordosis responsiveness thus appears to be due to some process other than release of pituitary hormones.