Shelton E. Hendricks

Lesions of the nucleus paragigantocellularis : effects on mating behavior in male rats

We evaluated the effects of bilateral radio-frequency lesions of the paragigantocellular (PGi) reticular nucleus in the ventral medulla on male rat copulatory behavior. In Experiment 1, sexually naive male rats with such lesions were more likely than sham-operated controls to copulate to ejaculation during their first exposure to an estrous female. Additionally, among the rats that copulated to ejaculation, those with lesions demonstrated a reduction in mount frequency (MF), intromission frequency (IF), and ejaculation latency (EL), and an increase in copulatory efficiency (CE). In Expt. 2, sexually experienced male rats were allowed to mate to sexual exhaustion. Males with PGi lesions showed an increased latency to sexual exhaustion and an increased number of ejaculations prior to exhaustion. Additionally, rats with PGi lesions displayed reductions in IF, EL, and post-ejaculatory interval (PEI) as they approached sexual exhaustion. Our results provide further evidence that the PGi is a supraspinal locus of descending inhibitory influence on spinal nuclei mediating ejaculatory reflexes in the male rat.

Effect of ovarian hormones on conflict behavior

We injected ovariectomized female rats with estrogen and progesterone. Some of the injection regimens used are known to induce estrus, while other do not. The effects of these treatments on operant behavior were evaluated. Operant behavior was maintained under a reinforcement schedule, one segment of which involved experimentally induced conflict. Such behaviors previously have been shown to be modified by anti-anxiety drugs. Those hormone treatments effective in inducing estrus had behavioral effects similar to the effects observed for established anti-anxiety agents. Hormone-injection regimens not capable of inducing estrus were without effect on operant behavior. Our findings suggest that the reproductive cycles of female rats are associated with behavioral changes which may be indicative of changing anxiety levels mediated in part by changing titers of ovarian hormones. We suggest that the evaluation of hormonal influences on operant behaviors sensitive to tranquilizers should be a useful model system for studying possible mechanisms underlying emotional changes associated with reproductive cycles.

Fluoxetine-induced inhibition of male rat copulatory behavior: Modification by lesions of the nucleus paragigantocellularis

In Experiment 1, the 5-HT uptake blocker fluoxetine (FLX; 20 mg/kg) reduced the proportion of sexually experienced male rats displaying ejaculations. Among those animals that did ejaculate there was an increase in intromission frequency (IF), ejaculation latency (EL), and postejaculatory interval (PEI) and a reduction in copulatory efficiency (CE) during the final copulatory sequence prior to sexual exhaustion. In Experiment 2, we found similar inhibitory effects of FLX as well as facilitating effects of lesions of the nucleus paragigantocellularis (PGi) on male rat copulatory behavior. Males with PGi lesions displayed more ejaculations and a longer latency to sexual exhaustion compared to intact animals. When FLX was given to rats with PGi lesions, it did not influence the proportion of rats ejaculating nor did it alter IF, EL, or PEI during the final copulatory series prior to exhaustion. These findings suggest that the inhibitory influences of FLX on male rat copulatory behavior are mediated in part by the interaction of FLX with neurons originating in the PGi.

Event-Related Potential Amplitude/Intensity Slopes Predict Response to Antidepressants

We measured event-related potential (ERP) component amplitudes to four intensities of randomly presented tones. Patients diagnosed with major depressive disorder were tested prior to and following a clinical trial of antidepressant medication. Slope of P2 amplitude as a function of stimulus intensity was calculated for each subject and condition. Subjects were divided into two groups (responders and nonresponders) based on their Hamilton Rating Scale for depression scores following treatment. Responders had significantly larger P2 slopes prior to treatment than did nonresponders. P2 slopes did not differ significantly between responders and nonresponders following antidepressant treatment. These data support the conclusion that P2 amplitude/intensity slope may be a predictor of response to treatment with antidepressant medication.

Antidepressants augment natural killer cell activity: In vivo and in vitro

Depressed mood has been associated with reduced natural killer cell activity (NKCA). Further, amelioration of depressive symptoms by pharmacotherapy has resulted in augmented NKCA. Serotonin, an indoleamine implicated in the pathophysiology of affective disorders, enhances NKCA in vitro and lymphocytes possess serotonin transporters and receptors. The present study evaluated NKCA in depressed outpatients before and during treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac®). Further, the SSRIs, fluoxetine and paroxetine (Paxil®), were also incubated in vitro with lymphoid cells to evaluate possible direct effects of SSRIs on NKCA. Depressed outpatients were administered fluoxetine (20 mg/day) for 4 weeks. NKCA and severity of depression were evaluated at weeks 0, 1, 2, and 4. Serum concentrations of fluoxetine and norfluoxetine were obtained as well. Mononuclear cells obtained from nonpatient volunteers were incubated with pharmacologic concentrations of fluoxetine or paroxetine and NKCA measured with a standard chromium release assay. Fluoxetine treatment resulted in decreased symptoms of depression and increased serum concentrations of fluoxetine and norfluoxetine. Further, fluoxetine treatment was associated with augmented NKCA in a subgroup of depressed outpatients exhibiting low NKCA at baseline. Fluoxetine had no effect on NKCA in depressed individuals exhibiting high NKCA at baseline. Incubation of mononuclear cells with fluoxetine and paroxetine augmented NKCA in vitro. The enhancing effects of antidepressants on NKCA in vivo and in vitro indicate a possible direct drug interaction with lymphoid cells during pharmacotherapy, suggesting that pharmacologic treatment of depression may result in enhanced immune competence as indexed by enhanced NKCA and that NKCA could be pharmacologically augmented with antidepressants in individuals with compromised immune function.

Anxiolytic effects of progesterone are sexually dimorphic.

We evaluated the effects of progesterone administration to estrogen-primed rats on licking behavior during a lick suppression test. This test assesses the behavior of water-deprived rats to lick a drinking tube for water reinforcement that is paired to electric shock. Chlordiazepoxide (a commonly used tranquilizer) is very effective in increasing licking during this test. Normal females and neonatally castrated males displayed an increase in shock-punished responses in tests conducted after hormone injections. Normal males and neonatally androgenized females were unaffected. Our results suggest that ovarian steroids, and particularly progesterone, can modulate anxiety in females and feminized males. In addition, the anxiolytic effect of progesterone appears to be mediated by a mechanism different from that of Chlordiazepoxide.

Multiple ejaculations and chronic fluoxetine: effects on male rat copulatory behavior.

Male rats were treated with fluoxetine (FLX) or vehicle daily for 14 days and copulatory behavior tested on day 15. Rats were either mated to three ejaculations or to sexual exhaustion. Both standard measures and the mount bout analysis were used to evaluate the effects of the chronic FLX on male rat copulatory behavior. Only 56.25% of the animals treated with FLX achieved three ejaculations. FLX inhibited the consumatory aspect of male sexual behavior, especially the ability to achieve three ejaculations, but there was no effect on the propensity of the male to pursue the female. These differences were observed for the first three ejaculations. Analysis of the last three ejaculations in those animals that mated to exhaustion did not reveal an effect of FLX. The behavioral pattern of FLX-treated animals during the first three ejaculations resembled that observed during the last three ejaculatory series in the vehicle-treated animals that mated to exhaustion. The results are discussed in terms of the serotonergic effects on male rat sexual behavior.

Monoaminergic influences on temporal patterning of sexual behavior in male rats

We evaluated the effects of the serotonin (5-HT) presynaptic uptake blocker fluoxetine (FLX) and the dopamine (DA)/noradrenaline (NE) releaser amantadine (AMA), separately and in combination, on the temporal patterning of male rat sexual behavior. FLX alone increased intermount-bout intervals, time-outs, grooming time, ejaculation latency, number of mounts per mount bout, and number of mount bouts per ejaculation. AMA alone had the opposite effect on these measures. Additionally, AMA, when given in combination with FLX, completely reversed the FLX-induced deficits in copulatory behavior. We interpret our results as suggesting an interaction between 5-HT and catecholamines in the temporal patterning of male rat copulatory behavior.

Prenatal Alcohol and Stress Interact to Attenuate Ejaculatory Behavior, but Not Serum Testosterone or LH in Adult Male Rats

Restraint stress reduced blood alcohol levels in pregnant rats given a liquid alcohol diet. The male offspring prenatally exposed to both stress and alcohol failed to ejaculate spontaneously, although they copulated normally following exogenous testosterone (T) administration. Males prenatally exposed only to alcohol or only to stress showed no behavioral deficits. Adult serum T and luteinizing hormone levels were normal in both of the fetal alcohol exposed male groups. It appears that the androgen threshold for ejaculatory behavior is elevated in males prenatally exposed to alcohol plus stress and cannot be realized with normal testosterone titers, but it can be attained with exogenous hormone administration. Presumably the alcohol and stress combination interfered with ontogenetic patterns of T needed to fully masculinize the fetal nervous system.

Modification of CAPS-1 for diagnosis of PTSD in Afghan refugees

A DSM-III-R based instrument for the assessment of posttraumatic stress disorder (PTSD), the Clinician-Administered PTSD Scale (CAPS-1), was modified to accommodate cultural differences and translated into the Afghan languages Pushto and Farsi (Dari) and administered to 30 Afghan refugees living in the United States. The modified CAPS-1 was found to be practical and reliable. Inter-item correlations were calculated on the frequency and intensity scores for the 17 cardinal symptoms and the eight associated features items of the modified CAPS-1. The four reexperiencing items demonstrated significant independence from the avoidance and arousal symptom clusters. However, the avoidance and arousal symptom clusters were not found to be independent cardinal components of PTSD in our participants. The CAPS-1 criteria for diagnosis of PTSD were met by 50% of the subjects evaluated.