Sexual impairment of inexperienced male rats following pre- and postpuberal olfactory bulbectomy.

Olfactory bulbectomy of sexually inexperienced male rats prevented the occurrence of sexual behavior in most of the operated animals. This effect was observed in rats bulbectomized before puberty as well as after puberty. Bulbectomized rats which had heterosexual experience prior to the operation did not deviate from intact rats. Males living in cohabition with intact males prior to the operation showed only minor deficits in their mating performances. It was concluded that the olfactory lobe while of only minor importance for maintenance of mating once sexual behavior has been initiated, plays an important role in initiation of sexual behavior of the male rat. Furthermore, since treatment with testosterone of prepuberally bulbectomized rats did not stimulate the animals to sexual activity it was concluded that the sexual impairment following bulbectomy of isolated males presumably is not due to an impaired production of gonadal secretions.     

Brain transplants enhance rather than reduce the impairment of spatial memory and olfaction in bulbectomized rats

The possibility to compensate the loss of olfactory and non-olfactory functions due to removal of the olfactory bulb by embryonal brain grafts was investigated in adult rats. Spatial working memory was examined in an 8-arm radial water maze task 6 weeks after bulbectomy. During 15 daily trials, performance gradually improved in bulbectomized controls (n = 10) and in rats with olfactory bulb transplants (n = 9), but did not attain that of intact controls (n = 10). No improvement was observed in the rats with substantia nigra grafts (n = 8). Eleven weeks after bulbectomy, the same rats were tested in the water tank navigation task. The performance improved during ten 12-trial sessions in bulbectomized rats less than in intact controls, but more than in the transplanted rats. The olfactory food retrieval test performed 14 weeks after bulbectomy revealed almost full recovery of smell in bulbectomized rats, but not in the transplanted animals. It is concluded that the spatial memory deficit is probably due to bulbectomy-induced interference with septohippocampal function which is not alleviated, but rather enhanced by transplantation. The results suggest that the effect of brain grafting is not always beneficial.     

Male copulatory behavior and female maternal behavior in neonatally bulbectomized rats

Olfactory bulbs were destroyed in six-day-old male and female rats, and anosmia was confirmed in adulthood. Bulbectomized males initiated apparently normal sexual activity at the same age as did control animals. As virgins, bulbectomized females did not injure foster young; when allowed to mate and deliver young, they displayed apparently normal maternal behavior. It was concluded that neonatal olfactory bulbectomy does not preclude the development of essentially normal copulatory behavior in the male rat and maternal behavior in the female rat.     

Corticosterone, choline acetyltransferase and noradrenaline levels in olfactory bulbectomized rats in relation to changes in passive avoidance acquisition and open field activity

Consequences of olfactory bulbectomy in two behavioural situations, passive avoidance acquisition and activity in a brightly lit open field, were measured in the same animals for which data on four biochemical measures were also obtained. The biochemical measurements were on plasma corticosterone levels, noradrenaline (NA) levels in the midbrain and amygdala + pyriform cortex and the choline acetyltransferase (CAT) levels in the olfactory tubercle. Experimental variation in age groups of rats (7 weeks and 3 months) and in post-bulbectomy periods (1, 2 and 4 weeks) was made. The deficit in passive avoidance as a consequence of olfactory bulbectomy was evident in all groups of young animals and in older animals one and two weeks post-bulbectomy but not in older animals four weeks after bulbectomy. An increase in open field activity was similarly observed in all groups except in the older animals four weeks after bulbectomy. In contrast to reports by other investigators the basal plasma corticosterone levels were not increased in bulbectomized animals nor did we observe any diminution of NA levels in the amygdala (+ pyriform cortex). CAT levels were slightly increased in older animals two weeks after bulbectomy. The absence of a change in the plasma corticosterone level after bulbectomy is discussed in relation to the notion that the olfactory bulbectomized rat is in some way relevant as a test model for predicting efficacy of potential antidepressant drugs.     

Bulbectomy and sensitivity to estrogen: Anatomical and functional specificity

In order to clarify the influence of the olfactory system on female sexual behavior, ovariectomized rats were given sham operations (SHAM), total bilateral olfactory bulbectomy (TBULBX), partial bulbectomy (PBULBX), anterior olfactory nucleus lesions (AON) or accessory olfactory bulb lesions (AOB), and tested for lordosis behavior. Only TBULBX resulted in increased sensitivity to estradiol benzoate (EB) in that lordosis quotients (LQ) were increased and rejection behavior decreased following administration of 2, 4 or 8 μg EB/kg/day for 3 days. Only TBULBX group rats were anosmic on 2 postoperative tests. TBULBX group rats showed very mild hyperresponsiveness on an emotionality test. Effects of TBULBX on LQ are not due to general sensory hyperresponsiveness or EB-induced hyperresponsiveness since no differences in the quality of lordosis occurred, and no differences occurred in latency to paw-lift on hot plate tests with or without EB. Heightened EB sensitivity in the TBULBX group is not due to adrenal steroids since following adrenalectomy and 8 μg EB/kg treatment, TBULBX group LQ scores were still elevated relative to those of SHAM controls. The LQ scores of PBULBX group rats were intermediate to those of SHAM and TBULBX group rats. Bulbectomy-induced alterations in sensitivity to EB as measured by the LQ do not appear to be due to alterations in “arousal” mechanisms in general. While deficits in olfactory perception might exacerbate the effect, it is unlikely that anosmia per se is sufficient to induce major alterations in the degree of sexual receptivity following EB. The magnitude of behavioral effects of bulbectomy on EB sensitivity may be related, to some extent, to the amount of bulb tissue removed. It is possible that bulbectomy may enhance behavioral sensitivity to EB by disrupting biochemical responses to EB in limbic system structures which normally exert an inhibitory influence over sexual receptivity.     

Effect of bilateral olfactory bulbectomy on discrimination avoidance conditioning in rats

Studies were made with the two-way shuttle box method on the acquisition of discrimination avoidance learning by olfactory bulbectomized rats in relation to changes in emotional behavior. Bulbectomized rats showed a marked increase in locomotor activity, with accompanying augmentation of the reactivity and the appearance of muricidal behavior. Initially, the bulbectomized rats showed elevated conditioned avoidance responses to both the CS+ and the CS-. In later stages, there was a continued slow increase in responses to the CS+ accompanied by a decrease in responses to the CS-, until responses to both stimuli were only slightly elevated above the levels shown by control rats. This result suggests that olfactory bulbectomy does not affect discrimination ability itself, but the impairment of discrimination during the initial stages is resulted from hyperemotionality induced by olfactory bulbectomy.     

Effects of olfactory bulb removal and flank shock on copulation in male rats

Sexually experienced male rats received bilateral olfactory bulbectomy (BOB, N=9), unilateral olfactory bulbectomy (UOB, N=7) or a sham operation (Sham, N=8). Copulation was severely disrupted in BOB males, whereas only minimal effects on copulation were observed in UOB males. Penile reflexes were not affected by either operation. Intermittent flank shock stimulated copulation in 5/6 BOB males. The BOB males that ejaculated had longer intromission latencies and longer postejaculatory intromission intervals than did Sham males receiving a similar schedule of shocks. Even so, all BOB males that ejaculated with flank shock also resumed copulation and ejaculated a second time without further shocks. Three BOB males that ejaculated with flank shock were tested the following week without shock, and none of these males copulated. These results strengthen previous conclusions that the olfactory bulbs are critical for the initiation and maintenance of sexual arousal in male rats.     

Effects of chronic activity wheel running and imipramine on masculine copulatory behavior after olfactory bulbectomy

We examined the effects of chronic activity wheel running and imipramine administration on appetitive behavior after olfactory bulbectomy (OBX). Male Long-Evans rats were randomly assigned to the following conditions using a 2 x 2 x 2 design: (1) bilateral OBX or sham surgery, (2) voluntary activity wheel running or sedentary home cage, and (3) daily imipramine or saline injections. After 21 days of treatment, animals underwent behavioral testing for copulatory activity and sucrose preference. Bulbectomized animals exhibited decrements in copulatory performance and reductions in sucrose intake compared to sham animals. Within the bulbectomized groups, imipramine-treated rats either did not copulate or had reduced ejaculation frequencies. However, activity wheel running attenuated the copulatory deficits induced by OBX. The findings encourage studies of physical activity and male sexual dysfunction among depressed men being treated by pharmacotherapy.     

Effects of ovarian hormones on sexual receptivity, proceptivity, and motivation in olfactory bulbectomized female rats.

The purpose of the present experiment was to assess the effect of olfactory bulbectomy and ovarian hormones on female sexual motivation. Ovariectomized female rats underwent either bilateral bulbectomy or sham surgery. Females received one of four subthreshold hormone treatments: 0% estradiol (E2) plus 500 micrograms progesterone (P), 100% E2 alone, 10% E2 plus 500 micrograms P, or 100% E2 plus 500 micrograms P. Sexual motivation (as indicated by a female's preference for a sexually active male over a castrated male) and proceptivity (dart and ear wiggling sequences) were measured in a three compartment partner preference apparatus. Sexual receptivity (lordosis) was measured separately in a glass arena with a sexually active male. Results showed that olfactory bulb removal facilitates sexual receptivity and proceptivity in females exposed to 10% or 100% E2 in combination with 500 micrograms P. In contrast, sexual motivation was only demonstrated by olfactory bulbectomized females which received 100% E2 in combination with 500 micrograms P. These findings support the hypothesis that olfactory bulbectomy induces a behavioral hypersensitivity to estrogen, and suggest that sexual motivation is an estrogen-mediated response which requires a higher level of estrogen stimulation than sexual receptivity and proceptivity.     

Role of aversively motivated behavior in the olfactory bulbectomy syndrome.

The aim of the present studies was to determine the extent to which changes in defensive behaviors could account for some of the behavioral effects of bilateral olfactory bulbectomy (OBX) in rats. Four tests of aversively-motivated behavior were conducted in bulbectomized and sham-operated rats: activity in a dimly lit or brightly lit open field, passive avoidance, foot shock-induced freezing, and defensive withdrawal. OBX reduced the duration of immobility in the open field. Bulbectomized rats exhibited less freezing in response to foot shock than sham-operated rats. In the defensive-withdrawal test, bulbectomized rats made more transitions into and spent less time inside the covered enclosure than sham-operated rats. The experiments thus reveal two novel paradigms for assessing the behavioral effects of OBX. The results also suggest that deficits in aversively-motivated behavior, specifically defensive freezing, may comprehensively explain the putative "hyperactivity" and "passive-avoidance learning deficits" widely associated with the OBX behavioral syndrome.     

Role of central alpha 2-adrenoceptors on the development of muricidal behavior in olfactory bulbectomized rats: effect of alpha 2-adrenoceptor antagonists

Upon surgical removal of olfactory bulbs, by the 8th to 10th day after the surgery muricidal behavior has been demonstrated in 75.4% of rats. In the homogenates of forebrain obtained from rats demonstrating muricidal behavior, levels of noradrenaline, 5-hydroxytryptamine and their metabolites (i.e., 3-methoxy-4-hydroxyphenylglycol sulfate and 5-hydroxyindoleacetic acid) were not changed. However, the fractional turnover rate of noradrenaline in the forebrain of the olfactory bulbectomized rats was significantly decreased without alterations in the metabolism of 5-hydroxytryptamine when compared to that of the sham rats. The muricidal behavior and the aggressiveness were suppressed by antagonists of alpha 2-adrenoceptors (yohimbine, idazoxan and rauwolscine), but not by the alpha 1-adrenoceptor antagonist (corynanthine). Furthermore, upon administration of yohimbine or idazoxan to rats demonstrating the muricidal behavior, the level of noradrenaline in the homogenates of forebrain was decreased while that of 3-methoxy-4-hydroxyphenylglycol sulfate was increased. The maximum binding capacity (Bmax) of [3H]yohimbine to the forebrain membranes obtained from the olfactory bulbectomized rats was significantly higher than that from the sham rats without demonstrating any differences in dissociation constants (Kd) between the two brain membranes. Based on these results, it was suggested that olfactory bulbectomy has caused some functional changes in central alpha 2-adrenoceptors.     

Olfactory control of the sexual behavior of male and female mice

Bilateral removal of the olfactory bulbs virtually eliminates sexual behavior in male and female mice. In the studies reported here, mice were rendered anosmic by intranasal application of a zinc sulfate solution. Peripherally induced anosmia did not affect the sexual behavior of male mice. Peripherally induced anosmia attenuated the hormone induced display of sexual receptivity in female mice, but peripherally anosmic females were significantly more receptive than bulbectomized females. This finding suggests that (1) pheromonal factors may be involved in the full arousal of sexual receptiveness in female mice, but (2) that the effect of bulbectomy upon sexual receptivity in female mice cannot be attributed solely to the surgical production of anosmia. The general failure of peripherally induced anosmia to mimic the effects of olfactory bulb removal upon the display of sexual behavior in male and female mice suggests that the olfactory bulbs are importantly involved in the control of sexual behavior in some manner not related to sense of smell.     

Olfactory bulbectomy: influences on maternal behavior in primiparous and multiparous rats

Bilateral olfactory bulb ablation resulted in deficits in several components of maternal behavior in lactating, primiparous female rats. These females frequently cannibalized pups shortly after parturition. Furthermore, bilaterally bulbectomized, primiparous females spent less time nursing their pups and retrieved fewer pups than unilaterally bulbectomized or sham-operated females. In contrast to the situation in primiparous females, in multiparous females bilateral bulbectomy failed to influence any parameter of maternal behavior.     

Influence of isolation and training on fighting in mice with olfactory bulb lesions

Isolation-induced aggressive mice receiving total bilateral bulbectomy failed to fight after chronic training. Animals receiving sub-total olfactory bulbectomy were capable of being trained to attack but the latency to attack was increased. When mice were bulbectomized before being isolated they were incapable of attack regardless of training or completeness of the lesion. These results indicated that isolation influences aggressive behavior in bilaterally bulbectomized mice.     

Simultaneous and successive olfactory bulb removal: influences on the mating behavior of male mice

Simultaneous olfactory bulb removal abolished mating behavior in sexually experienced male mice. In contrast to simultaneous bulbectomy, removal of both olfactory bulbs in two operations separated by an interval of 30 days had no effect on the mating behavior of male mice. In successively bulbectomized males, the occurrence or nonocurrence of the opportunity for mating behavior in the interval between the removal of each bulb had no influence on the degree to which mating behavior was spared. It was concluded that the abolition of mating behavior produced by simultaneously removing both olfactory bulbs in male mice is not a consequence of a sensory deficit, but is due to the destruction of tissues directly involved in the mediation of sexual behavior.     

Effects of early amygdaloid lesions on the initiation of interspecies aggression in the rat(author's transl)]

Bilateral amygdaloid lesions made at the age of 7–8 days entail a marked increase in the proportion of rats that display mouse-killing behavior when adult (90% killer-rats in a group sustaining extensive and symmetrical destruction of the amygdala, 65% killer-rats in a group sustaining more limited amygdaloid lesions, as compared to 9% killer-rats in the sham-operated group). Amygdaloid lesions that include the centromedial region are more efficient with regard to initiation of mouse-killing behavior than lesions that spare the central and medial nuclei. When performed at the age of 25 days, amygdaloid lesions also increase the proportion of killer-rats (62%, as compared to 17% in the sham-operated group). Amygdaloid lesions made at the age of 8 days clearly reduce the efficiency of early interspecific social contacts in preventing initiation of mouse-killing behavior (72% killer-rats among animals reared with mice from weaning). The efficiency of intraspecific social interactions in preventing initiation of mouse-killing behavior following removal of the olfactory bulbs is also reduced when bilateral amygdaloid lesions are combined with the bulbectomy at the age of 25 days (59% killer-rats, as compared to 7% killer-rats in a group of non-amygdalectomized bulbectomized animals). Intraspecific social interactions remain efficient in bulbectomized rats following a bilateral destruction of the dorsomedial thalamus.     

Olfactory bulbectomy depresses ultrasound production and scent marking by female hamsters

Female hamsters were observed for rates of ultrasound production, vaginal marking and flank marking before and after bilateral olfactory bulbectomy, unilateral bulbectomy or sham operations. Unilaterally bulbectomized and sham-operated subjects maintained preoperative levels of each behavior. In contrast, females with bilateral olfactory bulbectomies showed consistent decreases in rates of vocalization and scent marking. These results emphasize the dependence on an intact olfactory system of several courtship or agonistic behaviors that affect hamster reproduction by functioning as noncontact communications. Together with the results of previous studies suggesting that lordosis by female hamsters is unaffected by olfactory bulbectomy, these data also suggest differences in the brain and sensory mechanisms that control distinct types of reproductive behavior.     

Olfactory bulb removal: effects on sexual behavior and partner-preference in male rats

Control and bilaterally bulbectomized male rats were tested in an arena where the male could choose to spend time with (and mate with) a sexually receptive female, a nonreceptive female, or be in a neutral compartment. Control males mated with, and showed a strong preference for, sexually receptive females. Bulbectomy virtually eliminated mating. In addition, bulbectomized males showed no preference for a receptive female over a nonreceptive female, and spent their time equally between the receptive female, the nonreceptive female, and the neutral compartment. Effects of bulbectomy on preference and copulation could be consequences of a severely impaired ability to smell--the perception of odors may be essential for sexual arousal, or the absence of preference and copulation after bulbectomy might reflect a deficit in the male's ability to make odor-dependent classification of conspecifics as appropriate sexual partners. Or the behavioral effects of bulbectomy might reflect a disruption of tonic input to the forebrain that has little or nothing to do with the sensory impairment that follows bulb removal. But whatever the reason, in partner-preference tests bulbectomized males show a striking indifference to the sexual status of females, and it seems likely that the failure to mate is causally linked to this effect of surgery.     

Changes in amygdaloid afterdischarges and kindling effect following olfactory bulbectomy in the rat

Changes in the thresholds for afterdischarges and the formation of kindling effect in the medial amygdala following olfactory bulbectomy were investigated in the rat with chronic electrode implants. The threshold for afterdischarges in the amygdala of the olfactory bulbectomized rat (OB rat) was significantly decreased on day 4 after olfactory bulbectomy, however, no significant difference was found between OB and sham operated rats on days 7, 14 and 21 since the threshold in the sham group was also decreased at these periods after the surgery. The formation of kindling effect was remarkably accelerated in the OB rats. In this case, the number of days required to reach the stage 1 (Racine's classification) was significantly shortened. These results suggest that the activity of the medial amygdaloid nucleus is increased following olfactory bulbectomy.     

Hypoglycemia induced by olfactory denervation in turtle (Chrysemys d'orbigni)

Adult male turtles Chyrsemys d'orbigni with olfactory deficiency caused by olfactory deafferentation or by olfactory bulbectomy were used. Four, six and eight months later the lesioned turtles showed significantly lower blood glucose level than control animals. The hypoglycemia was similar in bulbectomized and deafferented turtles.