Fluctuations in neural activity during cocaine self-administration: clues provided by brain thermorecording

Since metabolic neural activity is accompanied by heat release, measurement of local brain temperature offers a method for assessing alterations in neural activity. This approach, continuous monitoring of local brain (ventral tegmental area, ventral striatum, and hippocampus) and body (temporal muscle) temperature, was used to study intravenous cocaine self-administration in trained rats. The first self-administration of a session was preceded by a strong temperature increase that continued after the drug infusion. After peaking at the time of the second self-administration, temperature plateaued (+0.7 degrees C) with biphasic fluctuations (+/-0.10-0.15 degrees C) around each subsequent self-administration. Temperature gradually increased before and for 30-50 s after the lever-press, but then abruptly decreased to a minimum at 180-240 s, when it began to increase to reach another peak immediately after the next lever-press. Doubling the dose of injected cocaine significantly potentiated the post-cocaine temperature decrease and increased time to the next lever-press. In contrast to drug-reinforced lever-presses, temperatures phasically increased after non-reinforced lever-presses and at the end of a session when the lever was blocked and the rat was hyperactive, trying to reach the inaccessible lever. While temperature changes in each recording location were generally correlative, the initial temperature elevation was stronger in all brain structures than in muscle and ventral striatum was the structure that showed the most pronounced and consistent temperature fluctuations. These data suggest a generalized brain activation associated with cocaine-seeking and cocaine-taking behavior with its phasic fluctuations around individual drug self-injections. While the initial component of brain activation preceding the first lever-press for cocaine is internally determined and closely related to behavioral search, subsequent biphasic fluctuations in neural activity associated with repeated drug intakes appear to be drug-mediated. Cocaine-induced potentiation of monoamine transmission is a possible factor for gradual increases in neural activity that drive cocaine seeking, while a rapid, brain concentration-dependent action on Na(+) transport (local anesthetic action) is the most probable factor determining an abrupt, transient cessation of neural activation associated with cocaine reward.     

Stress and sexual behavior in male rats

The relationship between sexual behavior and stress in male rats was investigated. Stress induction by psychophysical immobilization fo 3 hours along three days caused significant alterations of the different parameters which make up the sexual behavior of male rats. An extension of the stressing situation from 3 to 6 hours under the same experimental conditions produced very similar sexual disturbances. Our experimental results suggest that effects of acute stress on sexuality may be independent of time.     

Changes in forebrain Na,K-ATPase activity and serum hormone levels during sexual behavior in male rats

We have previously shown that Na,K-ATPase activity (the enzymatic machinery for the sodium pump) in brain areas such as the medial basal hypothalamus (MBH) and the preoptic-suprachiasmatic region (POSC) can be changed by experimental manipulations of gonadal function. We now report enzyme levels in brain regions as related to hormonal changes occurring during sexual behavior. Male rats were exposed to receptive females and decapitated immediately after displaying one of the following behavioral events: the start of copulatory activity, first ejaculation, and the beginning of a second copulatory series. A group of noncopulating animals were used as control. The variables measured included serum levels of LH, PRL and testosterone and Na,K-ATPase activity in MBH, POSC and parietal cerebral cortex (CC). A steady increase in enzyme activity in the POSC, but not the MBH or CC, was found in copulating animals. Serum LH levels changed in a similar fashion. A sharp increase in serum PRL levels, seemingly related to ejaculation, was also observed. These data are consistent with our previous findings on monoaminergic neurotransmission in brain regions related to male sexual behavior.     

Prefrontal electroencephalographic activity during the working memory processes involved in a sexually motivated task in male rats

The prefrontal cortex is involved in working memory functions, and several studies using food or drink as rewards have demonstrated that the rat is capable of performing tasks that involve working memory. Sexual activity is another highly-rewarding, motivated behaviour that has proven to be an efficient incentive in classical operant tasks. The objective of this study was to determine whether the functional activity of the medial prefrontal cortex (mPFC) changes in relation to the working memory processes involved in a sexually motivated task performed in male rats. Thus, male Wistar rats implanted in the mPFC were subjected to a nonmatching-to-sample task in a T-maze using sexual interaction as a reinforcer during a 4-day training period. On the basis of their performance during training, the rats were classified as ‘good-learners’ or ‘bad-learners’. Only the good-learner rats showed an increase in the absolute power of the 8–13 Hz band during both the sample and test runs; a finding that could be related to learning of the working memory elements entailed in the task. During the maintenance phase only (i.e., once the rule had been learned well), the good-learner rats also showed an increased correlation of the 8–13 Hz band during the sample run, indicating that a high degree of coupling between the prefrontal cortices is necessary for the processing required to allow the rats to make correct decisions in the maintenance phase. Taken together, these data show that mPFC activity changes in relation to the working memory processes involved in a sexually motivated task in male rats.     

Relation of autogrooming to sexual behavior in male rats

Grooming and penile reflexes were studied in male rats that were restrained in supine position with the penile sheath retracted or were free to copulate with sexually receptive females. In Experiment 1 there was a reliable concordance in supine males between the tendency to groom and the tendency to display penile reflexes. In Experiment 2 we analyzed the sequential organization of grooming and genital events in supine tests. It was assumed that many or most episodes of ventral grooming would have been genital grooming had access to the genitalia not been prevented by restraint. Paw grooming tended to precede clusters of penile responses, whereas ventral grooming started after the onset of erections. Experiment 3 was an exploration of grooming in the context of copulation, rather than supine restraint. Males groomed their genitalia immediately after all intromissions and after all mounts that ended mount bouts. The duration of grooming was not affected by whether or not intromission occurred. Finally, in Experiment 4 we observed genital and nongenital grooming and recorded electromyographic (EMG) activity from the striated bulbospongiosus muscle (mBS) of the penis in freely moving rats. Consistently, mBS activity led to genital grooming with a short latency, whereas nongenital grooming rarely led to genital grooming, and EMG activity was not associated with nongenital grooming nor did it tend to follow after genital grooming was initiated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostaglandin E2 accelerates sexual behavior in male rats

Sexual behavior in male rats is accompanied by an increase in body temperature of 18 degrees C. It has been suggested that this increase may be, at least in part, a febrile response mediated by the endogenous central release of prostaglandins of the E series (PGE). This putative release of PGE could also affect the expression of sexual behavior, a possibility that was tested in the present experiment. PGE2 was infused into the cerebral aqueduct and sexual behavior and hypothalamic temperature were monitored. PGE2 infusion raised hypothalamic temperature and decreased the postejaculatory interval and ejaculation latency. The exact cause of this acceleration of sexual behavior cannot as yet be determined.     

Hippocampal rhythmical slow activity during instrumental responses with sexual reinforcement in male rats

The hippocampal EEG activity was recorded in male rats during the response-contingent reinforcement of a female. The instrumental response was a bar-pressing on a fixed-ratio-10 reinforcement schedule. The frequency of bar-pressing tends to increase during the succeeding copulatory series. The similar phenomenon was observed in the frequency of the hippocampal slow activity (RSA) accompanying the bar-pressing and the pursuit of the female. This tendency was most conspicuously present during the first copulatory series but became less evident during the following ones.     

Activation of POMC neurons during general arousal but not sexual behavior in male rats

Exogenous opioids influence male rat sexual behavior, suggesting that endogenous opioid peptides are released during mating. Supporting this hypothesis, the authors recently showed that mating induced activation of mu opioid receptors. However, it is unknown which ligand(s) is acting on these receptors during mating. The current set of experiments tested the hypothesis that beta-endorphin-producing neurons, that is, proopiomelanocortin (POMC) neurons, are activated during sexual behavior. Mating-induced activation of POMC neurons was investigated during either the dark phase or the light phase, following different components of male rat sexual behavior or following control manipulations that resulted in general arousal. Results show activation of POMC neurons in the mediobasal hypothalamus following general arousal but not specifically related to sexual behavior per se. In addition, mating did not activate the subpopulation of POMC neurons that project to the medial preoptic nucleus. These results suggest that it is unlikely that POMC neurons contribute to the action of endogenous opioids in the brain area during sexual behavior but instead may contribute to the change in arousal state essential for the expression of sexual behavior.     

Effects of vasopressin on female sexual behavior in male rats

Intracerebroventricular (i.c.v.) injection of an Arg-vasopressin (AVP) antagonist did not stimulate female sexual behavior in adult castrated male rats treated with ovarian hormone but stimulated this behavior in male rats which were castrated on the day of birth. It is suggested that neonatal androgen stimulation in the male rat offsets the influence of AVP on female sexual behavior in the adult.     

Tail pinch induces sexual behavior in olfactory bulbectomized male rats

Adult male Long-Evans rats were subjected to bilateral olfactory bulbectomy, sham surgery or no treatment. Of 34 bulbectomized rats, 24 failed to ejaculate on either of 2 tests with a primed ovariectomized female. All control animals exhibited normal sexual behavior, and 10 bulbectomized animals ejaculated at least once during the 2 tests. Later histological examination revealed a relationship between size of lesion and extent of behavioral deficits. After a third test, 16 nonejaculatory animals were subjected to a tail pinch (TP) procedure, immediately followed by a fourth test. The remaining 8 nonejaculatory animals were tested similarly, but without tail pinch. Ten of the 16 tail pinch animals showed complete sexual behavior on the first test, while 2 additional animals began to copulate after a second TP procedure 4 days later. Only 1 of the 8 animals not receiving TP ejaculated on these tests. Thus, TP applied shortly before sexual behavior tests can induce copulation in some males whose behavior had been disrupted by olfactory bulbectomy.     

Hormonal regulation of brain circuits mediating male sexual behavior in birds

Male sexual behavior in both field and laboratory settings has been studied in birds since the 19th century. Birds are valuable for the investigation of the neuroendocrine mechanisms of sexual behavior, because their behavior can be studied in the context of a large amount of field data, well-defined neural circuits related to reproductive behavior have been described, and the avian neuroendocrine system exhibits many examples of marked plasticity. As is the case in other taxa, male sexual behavior in birds can be usefully divided into an appetitive phase consisting of variable behaviors (typically searching and courtship) that allow an individual to converge on a functional outcome, copulation (consummatory phase). Based primarily on experimental studies in ring doves and Japanese quail, it has been shown that testosterone of gonadal origin plays an important role in the activation of both of these aspects of male sexual behavior. Furthermore, the conversion of androgens, such as testosterone, in the brain to estrogens, such as 17beta-estradiol, is essential for the full expression of male-typical behaviors. The localization of sex steroid receptors and the enzyme aromatase in the brain, along with lesion, hormone implant and immediate early gene expression studies, has identified many neural sites related to the control of male behavior. The preoptic area (POA) is a key site for the integration of sensory inputs and the initiation of motor outputs. Furthermore, prominent connections between the POA and the periaqueductal gray (PAG) form a node that is regulated by steroid hormones, receive sensory inputs and send efferent projections to the brainstem and spinal cord that activate male sexual behaviors. The sensory inputs regulating avian male sexual responses, in contrast to most mammalian species, are primarily visual and auditory, so a future challenge will be to identify how these senses impinge on the POA-PAG circuit. Similarly, most avian species do not have an intromittent organ, so the projections from the POA-PAG to the brainstem and spinal cord that control sexual reflexes will be of particular interest to contrast with the well characterized rodent system. With this knowledge, general principles about the organization of male sexual circuits can be elucidated, and comparative studies relating known species variation in avian male sexual behaviors to variation in neural systems can be pursued.     

Fluctuations in testosterone levels of male rhesus monkeys during copulatory activity

We examined the effect of copulatory activity on testosterone levels in rhesus monkeys using an animal-worn, radio-activated blood sampling device which enabled us to collect samples without interrupting sexual behavior. Two animals showed significant increases in serum levels of testosterone averaging 108% and 203% above the pre-ejaculation baseline. A third animal showed little change in serum testosterone levels during sexual behavior. The data demonstrate that the technique of remotely activated blood sample collection may prove valuable in psychoendocrine research.     

Copulation-contingent aversive conditioning and sexual incentive motivation in male rats: evidence for a two-stage process of sexual behavior

Male rats were tested for sexual incentive motivation and for copulatory behavior during acquisition of a copulation-malaise association. One group received an injection of 20 ml/kg of 0.15 M LiCl 1 min after ejaculation with a capelin oil-scented female and the other group received saline. LiCl was administered independently of copulation to this group. The subjects in the conditioned group showed reduced sexual motivation after two conditioning sessions, and copulation was almost extinguished after five sessions. At a postconditioning test with an unscented female, there was no group difference with regard to sexual motivation but the conditioned group still showed suppression of copulatory behavior. These data show that sexual incentive motivation and copulatory behavior can vary independently and that the associations copulation-malaise and scented female-malaise had been established during conditioning.     

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.     

Age-related deficits in brain androgen binding and metabolism, testosterone, and sexual behavior of male rats

Brain androgen binding and metabolism, serum testosterone (T), and sexual behavior were measured in old and young male Fischer 344 rats. After completion of sexual behavior tests, blood was collected for T assay and brains were removed for simultaneous measurements of cytosolic (ARc) and nuclear (ARn) androgen receptors and aromatase activity (AA) in the preoptic area (POA), hypothalamus (HYP) and amygdala (AMG). In Experiment 1, old and young intact males were examined. None of the old males ejaculated in any of the tests of sexual behavior whereas all of the young males ejaculated. The old males had lower levels of serum T, lower levels of ARn in the POA and HYP and lower levels of AA in the POA. The ARc levels of the old and young males did not differ. Experiment 2 was designed to determine if the deficits in brain androgen binding and metabolism were due to low levels of T. Old and young T-treated gonadectomized (GX-T) males and young intact (I) males were examined. T levels were comparable in the young and old GX-T males and were higher in each of these groups than in the young I males. In sexual behavior tests, all of the young but only 25% of the old GX-T males ejaculated. Although ARn levels in the old GX-T males were lower than in the young GX-T males, they were comparable to the young I male levels. No age-related differences in T induction of AA were observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of bicuculline on sexual activity in castrated male rats

The GABA antagonist (+) bicuculline methiodide (30 ng/cannula) was injected in the medial preoptic-anterior hypothalamic area of castrated rats treated with subthreshold dosages of testosterone propionate (150 micrograms/kg/day). The treatment resulted in a facilitation of sexual activity suggesting a role of GABA as a neurotransmitter in neural processes determining sexual arousal.     

Nuclear estrogen receptor binding in microdissected brain regions of female rats during pregnancy: Implications for maternal and sexual behavior

Previously, we showed that changes in nuclear estrogen receptor (NER) concentrations within large dissections of the preoptic area and hypothalamus of pregnant rats might underlie changes in both maternal and sexual behaviors. To more precisely localize these biochemical changes, NER concentrations were measured in microdissected nuclei within the preoptic area and hypothalamus of pregnant rats on days 8, 16 and 22. Results indicated that NER levels changed significantly throughout pregnancy and that the magnitude and direction of change was site specific. Although a different pattern of change was found in each nucleus, NER levels in most preoptic area nuclei were significantly higher by the 16th day of pregnancy compared to those on day 8, while receptor levels in most hypothalamic nuclei did not increase until day 22 of pregnancy. The higher NER levels found in preoptic area nuclei of female rats as pregnancy advances can be correlated with growing maternal responsiveness during pregnancy, while elevated concentrations of NER in hypothalamic nuclei at the end of pregnancy may indicate preparation for postpartum estrus.     

Aversive behavior during intraoral intake in male rats

We investigated if the taste of a sucrose solution becomes progressively more aversive during intraoral infusion and if this contributes to the termination of the intake in male rats. The display of aversive behavior, such as gapes and chin rubs, but not headshakes, forelimb flails or orofacial grooming, varied with the concentration of an intraorally infused solution of quinine hydrochloride (QHCl) and increased by the time the rat rejected an intraorally infused 2 M solution of sucrose. Activation of gapes and chin rubs by brief intraoral infusion of QHCl advanced the rejection of the sucrose solution if given late during intraoral infusion, but blockade of gaping by anaesthesization of the oral cavity with Xylocain did not prolong the intake of the sucrose solution. Headshakes and forelimb flails could be elicited by stimulating the head and limbs with sucrose, and gapes and chin rubs were activated by infusion of a 2 M solution of sucrose into the stomach or duodenum but not by infusion of glucose into the jugular or hepatic portal vein. Preventing filling of the gastrointestinal tract during intraoral infusion of sucrose (sham feeding) eliminated the display of gapes and chin rubs. It is suggested that an increase in the aversiveness of the taste of a sucrose solution contributes to the rejection of that solution during intraoral infusion. However, rats can reject a sucrose solution in the absence of any behavioral sign of aversion and none of the so-called "taste-related" aversive behaviors is exclusively dependent upon stimulation of the taste receptors in the oral cavity.