Carlos Beyer

Hyperalgesia induced by altered glycinergic activity at the spinal cord

Glycine or its receptor antagonist, strychnine, were administered perispinally to investigate their effect on nociceptive responses elicited by activation of various cutaneous receptors. Strychnine produced dose-dependent sensory and motor disturbances; 1 and 5 micrograms doses were sub-convulsive, eliciting recurrent episodes of coordinated grooming, scratching and biting at the skin, which persisted for approximately 10 minutes post-injection; higher doses (25 and 100 micrograms) increased the intensity and duration of these effects, and produced convulsive motor seizures. Motor disturbances were not elicited by glycine (5, 25, 100 and 400 micrograms). Strychnine treated rats, at all doses, vocalized consistently in response to light cutaneous stimulation; a significant proportion of glycine treated rats also vocalized, but were not as sensitive to mild stimulation. Skin hyperalgesia persisted for at least 30 minutes in both strychnine and glycine treated rats. Both strychnine and glycine significantly reduced vocalization thresholds to tail shock. However, no clear effect on tail flick latency was observed following either strychnine or glycine. These results indicate that glycinergic neurons contribute to the tonic regulation of nociceptive input at the spinal cord.

Nociceptive responses to altered gabaergic activity at the spinal cord

GABA agonists and antagonists were injected intrathecally at the spinal cord, to determine their effect on nociceptive thresholds. Tactile stimulation, applied against the flank by a medium diameter von Frey fiber (5.5 g force), elicited distress vocalizations after, but not before injection of the GABA antagonists, bicuculline MI or picrotoxin (0.25 and 1 microgram dosages). Vocalization threshold to tail shock was significantly reduced by bicuculline MI or picrotoxin. Tail flick withdrawal latency from radiant heat was not altered by GABA antagonists. The GABA agonist, muscimol, significantly elevated vocalization threshold to tail shock at a 5 micrograms dose. At a lower dose level (1 microgram), muscimol significantly reduced vocalization threshold to tail shock. Tail flick latency was significantly prolonged by the 5 micrograms dose of muscimol; however, flaccid paralysis of the hind limbs was also evident. Nociceptive thresholds were not altered by GABA or saline injection. These findings indicate that GABAergic activity contributes to the tonic modulation of nociception at the spinal cord.

Androgen structure and male sexual behavior in the castrated rat

Abstract The following androgens were injected sc (1 mg for 30 days) to groups of inexperienced castrated male rats: testosterone, androstenedione, androstenediol, dehydroepiandrosterone, 11 β-hydroxy-androstenedione, androsterone, dihydrotestosterone, androstanedione, androstanediol, and 5 β-androstanediol. The mating tests were performed every third day. Only testosterone, androstenedione, and androstenediol elicited the full mating pattern. Both 5 a and 5β reduced androgens were ineffective in stimulating clear sexual behavior. In contrast, two 5 a reduced androgens, androstanediol and dihydrotestosterone, were the most potent androgens to induce growth of the sex accessories. The results suggest that 5 a reduction does not play a role in the action of androgens on the brain structures related to the expression of sexual behavior in the male rat, and that the stereochemical characteristics of the androgen molecule required to elicit sexual behavior are different from those involved in androgenicity.

Responses of diencephalic neurons to olfactory bulb stimulation, odor, and arousal

Summary Neuron populations in the lateral hypothalamus, medial thalamus, and dorsal periventricular diencephalic region along the projection pathways of the medial forebrain bundle and stria medullaris-inferior thalamic peduncle, were activated by electrical stimulation of the olfactory bulb in urethane-anesthetized rats. Fifty-seven percent of these neuron populations were also activated by xylene vapors. The median response latency of hypothalamic neurons to single pulses was 10 msec (range: 4–16 msec) and that of thalamic neurons was 14 msec (range: 4–21 msec). Stimulus trains activated neuron populations at substantially longer latencies as well as at these short latencies. The most common types of response were excitation, and excitation followed by activity suppression followed by re-excitation. Responses were usually recorded ipsilaterally to the stimulation site, but were also obtained contralaterally. They were blocked by transection of the lateral olfactory tract. The neuronal responses to olfactory bulb stimulation and xylene, even very short latency responses, were strongly modified in relation to arousal level, as monitored by the cortical EEG.

GABAergic Control of Receptivity in the Female Rat

GABAergic neurotransmission has been implicated in the control of the steroid-dependent behavior, lordosis. GABA has dual effects on lordosis: it facilitates lordosis through actions in the medial hypothalamus (mHYP) and it inhibits lordosis through actions in the preoptic area (POA). In the present study, gonadally intact and ovariectomized female rats were behaviorally tested with a sexually active male. Brains were removed from sexually receptive female either 1 or 24 h after behavioral testing. There was a significant difference in endogenous GABA concentration in HYP and POA between receptive, postreceptive and ovariectomized nonreceptive females. Specifically, GABA levels in postreceptive females were higher in the HYP (20%) and lower in the POA (21%) in comparison to receptive females (p less than 0.05). There was also a significant change in binding parameters of 3H-muscimol in the HYP and POA of receptive females as compared to 24 h postreceptive and ovariectomized rats. Attempts to modulate 3H-GABA release from hypothalamic tissue slices by estrogen or progesterone in ovariectomized rats yielded no effect on this parameter.

Facilitation of lordosis behavior in the ovariectomized estrogen primed rat by dibutyryl cAMP

Abstract The effect of systemic administration of various dosages of db cAMP (0.5, 1, 2, 8 and 16 mg) on the sexual behavior of ovariectomized estrogen primed rats (2 μg of EB administered 44 hours before dibutyryl cAMP) was studied. All but the low dose of db cAMP elicited lordosis in at least 50% of the rats. The response to db cAMP varied greatly among subjects. No dose response relationship was observed within the dose range of db cAMP employed. Theophylline (10 mg) administered simultaneously to db cAMP increased and prolonged the action of the nucleotide. Bilateral infusion of 50 μg of db cAMP into the medial preoptic area of estrogen primed rats elicited lordosis behavior in four out of eight animals. Dibutyryl cAMP did not produce sequential inhibition. The results suggest that a rise in the intracellular level of cAMP is involved in the hormone facilitation of sexual behavior in estrogen primed rats.

Differential effect of testosterone and dihydrotestosterone on the sexual behavior of prepuberally castrated male rabbits

Abstract The effect of testosterone propionate (Tp) and dihydrotestosterone propionate (DHTp) at doses of 1, 3 and 9 mg daily for 30 days on the copulatory behavior of prepuberally castrated male New Zealand white rabbits was studied. Tp was significantly more effective than DHTp in eliciting copulatory behavior at each dose level tested. Three milligrams Tp was the minimal dose required to elicit mounting consistently. DHTp at the high dose level (9 mg) only elicited sexual activity comparable to that observed with the low dose of Tp (1 mg). The results suggest that T does not need to be reduced to DHT to stimulate sexual behavior in the male rabbit.

Lordosis facilitation in estrogen primed rats by intrabrain injection of pregnanes

Progesterone (P) and nine of its natural metabolites were bilaterally injected (5 micrograms in 0.5 microliter oil) into either the ventromedial hypothalamus (VMH) or the medial preoptic area (MPOA) of estrogen primed rats to assess their relative potencies for stimulating lordosis. P, 5 alpha-pregnanedione and 5 beta, 3 beta-pregnanolone elicited lordosis when injected at either VMH or MPOA. By contrast, 5 alpha, 3 beta-pregnanolone as well as 20 alpha-OH and 20 beta-OH-pregnenone were much more effective in stimulating lordosis when implanted in the MPOA. Finally, 5 beta-pregnanedione and 5 beta,3 alpha-pregnanolone did not stimulate lordosis at neither VMH nor MPOA. The observation that lordosis was induced in estrogen primed rats both by pregnanes that bind to the P receptor (i.e., P; 5 alpha-pregnanedione; 20 alpha- and 20 beta-OH-pregnenone) and by pregnanes that do not (i.e., 5 alpha, 3 beta-; 5 beta,3 beta- and 5 alpha,3 alpha-pregnanolone) indicates that diverse cellular mechanisms are involved in the facilitation of lordosis by pregnanes.

Effects of diverse androgens on estrous behavior, lordosis reflex, and genital tract morphology in the rat☆

Abstract The effects of diverse androgens in selected dosages (testosterone propionate, 2 or 6 mg/day; 5-α-dihydrotestosterone, 2 or 6 mg/day; androsterone, 5 or 15 mg/day; androstendione, 5 or 15 mg/day) and estradiol benzoate (2 or 6 μg/day) were observed on the estrous behavior, lordosis reflex, and genital tract development of ovariectomized Sprague-Dawley rats. Steroids were injected for 10 days. Testosterone propionate was the only androgen to clearly stimulate estrous behavior (four of eight rats mated after receiving 6 mg/day TP). Estradiol benzoate at 2 μg, and 6-μg dose levels stimulated lordosis behavior in 50% and 100% of the subjects, respectively. No androgen induced clear vaginal cornification. All androgens except androsterone increased uterine weight and thickness of the myometrium. Only testosterone propionate (6 mg/day) induced a marked stimulation of the epithelium of the endometrium. The results suggest that the structural requirements of the androgen molecule for stimulating sexual behavior differ from those determining uterine growth responses.

A polygraphic analysis of mounting and ejaculation in the New Zealand white rabbit.

The duration and intensity of some components of the male copulatory pattern was studied in ten male (seven experienced, three inexperienced) and two female New Zealand white rabbits by using high speed cinematography, accelerometry and by recording the pressure of the seminal vesicles. Duration of mounts varied greatly within and among subjects. Effective mounts, i.e., those terminating in ejaculation, lasted less (2.61 +/- 1.50 sec, mean +/- SD; n, 59) than ineffective mounts (3.08 +/- 2.16 sec, mean +/- SD; n, 199). Frequency of pelvic thrusting was significantly higher in effective (13.54 +/- 1.11 sec, mean +/- SD; n, 59) than in ineffective mounts (12.08 +/- 0.98 sec, mean +/- SD; n, 176). No pelvic thrusting occurred during intromission which usually lasted less than one second (722 +/- 266 msec SD; n, 43). Shortly after intromission (230 +/- 107 msec, mean +/- SD; n, 32) the pressure of the seminal vesicles raised. This rise in pressure outlasted copulation (1040 +/- 369 msec, mean +/- SD; n, 32). The mounting pattern of inexperienced rabbits was similar to that of experienced rabbits. The mounting pattern of females differed from that of males both in rate of pelvic thrusting and duration of pelvic thrusts.