Serotonergic influences on EEG synchronization induced by milk drinking in the cat

Milk drinking elicits electroencephalographic (EEG) synchronization in the parieto-occipital cortex of cats. This EEG change is a reliable correlate of the consummatory phenomena involved in "relaxation" behavior. The effect of varying serotonin brain levels by administering P-chlorophenylalanine (PCPA) or 5-hydroxytryptophan (5HTP) on this response was studied in 25 young cats. Single or repeated injections (4-8 days) of 50, 100 or 150 mg/kg of PCPA resulted in a dose related decrease in the duration of the EEG parieto-occipital synchronization during fixed periods of milk drinking. A single injection of 3, 10 or 30 mg/kg of 5HTP to chronic PCPA treated cats, restored the EEG parieto-occipital synchronization during milk drinking to control values. Moreover, administration of 5HTP to non-treated cats significantly increased the duration of EEG parieto-occipital synchronization during milk drinking. Our results suggest that brain serotonergic neurons are involved in the development of EEG synchronization during milk drinking.     

Phasic activity induced by p-chlorophenylalanine in the auditory pathway

During paradoxical sleep, large amplitude phasic activity is found in different areas of the nervous system. This activity can also be pharmacologically induced by either reserpine or p-chlorophenylalanine (PCPA). Recently, this phenomenon has been reported at the level of the auditory pathway during paradoxical sleep and after the administration of reserpine. Thus, it was considered likely that this activity was qualitatively similar to that recorded in other brain structures and that it might be induced by PCPA as well. It was found that PCPA induced the appearance of phasic activity in structures of the auditory pathway that were recorded (cochlear nucleus and auditory cortex), as well as in those of the visual pathway (lateral geniculate body and visual cortex). Furthermore, total insomnia was produced between 48 and 72 hr after the injection of the drug, being most intense after the administration of a double dose (2 × 300 mg/kg). It is suggested that this phasic activity forms part of a common system together with that which has been recorded in other regions under similar physiological conditions.     

Methylphenidate Modifies the Motion of the Circadian Clock

People with attention-deficit/hyperactivity disorder (ADHD) often experience sleep problems, and these are frequently exacerbated by the methylphenidate they take to manage their ADHD symptoms. Many of the changes to sleep are consistent with a change in the underlying circadian clock. The present study was designed to determine if methylphenidate alone could alter properties of the circadian clock. Young male mice were examined in light–dark cycles and in constant darkness and recordings were performed on behavioral activity, sleep, and electrical activity in the suprachiasmatic nucleus (SCN) of freely moving mice. Methylphenidate in the drinking water (0.08%) significantly increased activity in the mid-to-late night, and led to a delay in the onset of activity and sleep relative to the light–dark cycle. While locomotor levels returned to baseline after treatment ended, the phase angle of entrainment required at least a week to return to baseline levels. In constant darkness, the free-running period of both wheel-running and general locomotor rhythms was lengthened by methylphenidate. When the treatment ended, the free-running period either remained stable or only partially reverted to baseline levels. Methylphenidate also altered the electrical firing rate rhythms in the SCN. It induced a delay in the trough of the rhythm, an increment in rhythm amplitude, and a reduction in rhythm variability. These observations suggest that methylphenidate alters the underlying circadian clock. The observed changes are consistent with clock alterations that would promote sleep-onset insomnia.     

Effects of a single dose of 3,4-methylenedioxymethamphetamine on circadian patterns, motor activity and sleep in drug-naive rats and rats previously exposed to MDMA

Rationale Despite the well documented neurochemical actions of 3,4-methylenedioxymethamphetamine (MDMA), acute effects in rats previously exposed to the drug have not been extensively explored.Objective To examine motor activity and vigilance effects of MDMA in drug-naive rats and in rats exposed to the drug 3 weeks earlier.Methods MDMA (15 mg/kg, IP) was administered to Dark Agouti rats. Motor activity, wakefulness, light slow wave sleep (SWS-1), deep slow wave sleep (SWS-2) and paradoxical sleep (PS), sleep and PS latencies were measured. Acrophases and amplitudes of the 24 h cycles were calculated by cosinor analysis. In parallel groups, local cerebral glucose utilization (lCMR_glu) and (³H)-paroxetine binding were measured in motor areas of the brain.Results In drug-naive rats MDMA caused marked increases in motor activity and wakefulness for at least 5–6 h. Circadian patterns of motor activity and sleep/vigilance parameters were altered up to 5 days after treatment. Despite most parameters tending to return to normal, there were still significant effects of MDMA on motor activity, wakefulness, and SWS-2 28 days later. Acute MDMA administration caused significant increases in lCMR_glu, but after 3 weeks lCMR_glu was decreased in the same brain areas. No significant change in [³H]paroxetine binding was observed in motor areas, although significant reductions were seen elsewhere (neocortex –81%). In rats exposed to MDMA 3 weeks earlier, most acute effects induced by MDMA administration were similar to those in drug-naive rats, but shorter duration of the acute effects were found in motor activity and vigilance.Conclusions Our findings provide evidence that MDMA use can lead to long-term changes in regulation of circadian rhythms, motor activity and sleep generation.     

Circadian rhythm-dependent development of melatonin effects and tolerance to PHNO in rats

Male Sprague-Dawley rats were given 12 days of continuous infusions of (+)-4-propyl-9-hyroxynapthoxazine (PHNO, 5microg/h), a highly selective dopamine D(2) receptor agonist, via subcutaneous ALZET((R)) osmotic pumps. Motor stimulant effects (locomotion and rearing) were monitored throughout the treatment period, including after the animals were injected with 2-iodo-melatonin (0.5 mg/kg) on days 8-10 and 13 after initiation of PHNO infusions. The rats (maintained on 12 L:12 D cycle) developed tolerance to the motor stimulant effects of PHNO during the day, and behavioral sensitization to PHNO during the night. Arousing rats with a vehicle injection transiently blocked the daytime tolerance. A more sustained environmental noise without handling of animals, which had a stronger effect on increasing motor activity of control rats, reversed tolerance to sensitization. Therefore, graded levels of arousal produce graded increases in motor activity in rats otherwise tolerant to the effects of PHNO. Daytime tolerance to PHNO was reversed to sensitization by 2-iodo-melatonin. This effect was more than an additive effect of drug + injection procedure stress. The differential development of nocturnal sensitization and diurnal tolerance to PHNO effects on motor activity may depend upon circadian rhythms in melatonin release, as well as on state of arousal.     

Diurnal rhythms in quinpirole-induced locomotor behaviors and striatal D2/D3 receptor levels in mice

Dopaminergic drugs, including the D2/D3 agonist quinpirole, produce lasting changes in the brain that lead to altered behavioral responses. The action of these drugs is dosing time-dependent; in fruit flies, behavioral response to quinpirole shows a marked circadian variability. Here we demonstrate diurnal rhythm-dependent variations both in quinpirole-induced locomotor behaviors and in striatal D2 and D3 protein levels in mice. We found opposing diurnal rhythms in striatal D2 and D3 protein levels, resulting in a high D2/D3 ratio during the day and a low D2/D3 ratio at night. Protracted quinpirole treatment differentially altered striatal D2/D3 rhythms depending on the time of injection (i.e., day or night). When quinpirole-induced locomotor activity was analyzed for 90 min, we found hypomotility after the first day or nighttime drug injection. By the seventh injection, daytime quinpirole treatment produced clear hyperactivity while nighttime quinpirole treatment continued to induce a significant initial hypoactivity followed by a hyperactivity period. Our data indicate that quinpirole-induced long-term alterations in the brain include dosing time-dependent changes in dopamine receptor rhythms. Therefore, we propose that diurnal mechanisms, which participate in drug-induced long-term changes in the dopamine system, are important for the development of dopaminergic behaviors.     

Circadian rhythms of body temperature and drinking and responses to thermal challenge in rats after PCPA.

Body temperature (Tb) and drinking were measured for five days in male and female rats. On day 6 (S1) the rats were injected with saline. On day 7 (P1) they were injected with PCPA (300 mg/kg IP). Measurements continued for 12 days. Immediately after PCPA Tb dropped. After that, the amplitude of the daily Tb rhythm was significantly decreased from days P2-P5. Females were more affected than males. Nocturnality of drinking was decreased on days P2-P4. Because the peak of the Tb rhythm advanced after PCPA, while the peak of the drinking rhythm was delayed, we conclude that the attenuation of the Tb rhythm was a direct result of PCPA treatment rather than a masking effect due to the attenuation of other rhythms. Other rats were thermally challenged during the first week post-PCPA. There were no differences in ability to regulate Tb in the cold, and the small variations in the heat were overshadowed by gender differences.     

The effect of fenfluramine on the microstructure of feeding and drinking in the rat.

1. The effects of three doses of fenfluramine on feeding and drinking in the rat were examined. 2. Feeding and drinking were subdivided into meals and bouts, and the changes in feeding/drinking were expressed in terms of meal/bout frequency, meal/bout size, meal/bout length, and eating/drinking rate. 3. The changes in these parameters were examined over different time periods after the injection. 4. Significant changes in the distribution of inter-response intervals within meals were found in time period 1 with 5 mg/kg and 10 mg/kg doses of fenfluramine. Videotape and computer analysis showed that the changes in inter-response interval histograms differed significantly from those seen in normal animals approaching satiety. Drinking parameters also changed. 5. Compensatory increases in feeding were observed in time period 4 with the 10 mg/kg dose. 6. The difficulties in designing and interpreting experiments in feeding are discussed, and the action of fenfluramine as an anorectic drug is considered.     

Effects of PCPA on the consumption of alcohol, water and other solutions.

The influence of para-chlorophenylalanine (PCPA) on the preference for alcohol, saccharin, glucose, and sodium chloride solutions and on water intake was studied in rats. Ten daily intragastric doses of 100 mg/kg PCPA were found to reduce alcohol preference both during and after PCPA treatment. Administration of daily 20 mg/kg IP doses of 5-hydroxtryptophan (5-HTP), plus a peripheral decarboxylase inhibitor, failed to reverse the PCPA-induced suppression in the post-PCPA test. Alcohol preference was not reduced below baseline following PCPA if this drug was administered between preference tests rater than coincident with alcohol drinking. Preference for saccharin, glucose, and sodium chloride solutions were all affected by PCPA. Large increases in water intake were produced by 50, 100, or 200 mg/kg PCPA given orally for 10 days. These experiments suggest that alcohol preference, in studies where PCPA treatment and alcohol drinking occur concurrently, may be considerably influenced by learned aversions to alcohol. Also, PCPA may, under some circumstances, produce an increased consumption of water by rats.     

General pharmacological action of 4-(o-benzylphenoxy)-N-methylamine hydrochloride (bifemelane hydrochloride, MCI-2016)--influence on the central nervous system

General pharmacological action of 4-(o-Benzylphenoxy)-N-methylbutylamine hydrochloride (bifemelane hydrochloride, MCI-2016) was examined with regard to the effects mainly on the central nervous system. MCI-2016, at 30-100 mg/kg, p.o., only showed a weak sleep prolongation effect (mice), anti-convulsant action (mice) and a moderate facilitation of exploratory behavior, but produced no remarkable behavioral changes. Above the doses of 200 to 300 mg/kg, p.o., MCI-2016 produced a decrease in muscle or body tone, mydriasis and a slight decrease of locomotor activity. The drug, however, showed little influence on exploratory behavior, conditioned avoidance response and normal body temperature (rats). Normal body temperature in rabbits was also little affected by MCI-2016. Effects on EEG was characterized by moderate activation of spontaneous EEG and potentiation of arousal response by stimulation of the midbrain reticular formation (1.5-5 mg/kg, i.v.). The drug, however, did not significantly change the sleep-wakefulness cycle and REM-sleep in rats. MCI-2016 also showed little influence on spinal reflex potentials and neuromuscular junction at high doses (10 mg/kg, i.v.). These results may indicate that MCI-2016 has slight influence on overall behavioral and motor changes. Effects of MCI-2016 on acetic acid-induced writhing, carrageenin edema and corneal reflex were also examined. MCI-2016 showed moderate analgesic and anti-inflammatory actions at 50-100 mg/kg, p.o., and also showed local anesthetic action. The duration of local anesthetic action was relatively long but the drug produced no local damage.     

Acute effects of toluene on circadian rhythms of sleep-wakefulness and brain monoamine metabolism in rats

Acute effects of a single i.p. injection of toluene on circadian rhythms of sleep-wakefulness were investigated in rats which were chronically implanted with EEG and EMG electrodes for polygraphic recordings. The toluene injection produced an initial increase in wakefulness (W) and a subsequent increase in slow-wave sleep (SWS) during the dark period. In an attempt to clarify mechanisms of these biphasic effects of toluene on sleep-wakefulness rhythms, brain monoamines and their metabolites were determined at the times of the initial increase in W and the increased SWS. The initial increase in W was associated with an increase in cortical NA, MHPG and 5-HT together with a decrease in cortical 5-hydroxyindoleacetic acid (5-HIAA), while the increased SWS during the dark period was associated with an increase in 5-HIAA and a concomitant decrease in 3-methoxy-4-hydroxyphenylglycol (MHPG). The toluene-induced changes in sleep-wakefulness seemed to be manifested at lower blood levels of toluene than the behavioral signs of central nervous system (CNS) depression. These biphasic effects of toluene on circadian sleep-wakefulness rhythms are discussed in terms of the reciprocal interactions between central 5-HT and NA neurons.     

Release of endogenous catecholamines from rat hypothalamus in vivo related to feeding and other behaviors

The release of endogenous noradrenaline (NA) and dopamine (DA) from various sites in the hypothalamus was determined in unanesthetized, freely moving rats by means of a push-pull perfusion technique in combination with a sensitive radiochemical assay. The perfusate was collected continuosly over 10-min periods for 4 to 8 hr. Patterns of feeding, drinking, grooming, and locomotor activity were recorded during the perfusion experiments. Release patterns and behavior recordings were analysed by tests of serial correlation. Although significant variations in catecholamine release over time were observed, they did not reflect a fixed autonomic periodicity. Release from the medial hypothalamus was measured in rats which had been deprived of food for 16 hr and were subsequently given free access to food. Before food presentation, mean NA release over 10-min periods was consistently higher than during satiety. Mean NA and DA release over 10-min periods before, during and after the occurence of feeding, drinking or grooming were calculated for the dorsomedial, perifornical, subfornical, and anterolateral hypothalamus of freely feeding rats. During feeding, NA (but not DA) release from the dorsomedial and perifornical areas was significantly elevated (40–50%) when compared with pre- or postfeeding values. An increase in catecholamine release was not observed during drinking or grooming. In addition, NA release from the anterolateral area correlated with locomotor activity. The enhancement of NA release from the perifornical area during feeding is considered to be specific as no change in release was observed even during the drinking vigorous response induced by angiotensin.     

State-dependent action of cocaine on brain temperature and movement activity: implications for movement sensitization

Because neural activity is highly energy consuming and heat producing, brain temperature offers a reliable, real-time measure of an animal's activity state and its changes induced by environmental and drug challenges. Therefore, it allows evaluation of the activity state of an animal preceding drug administration and its relation to subsequent drug-induced neural effects. This approach was used to explore the state dependency of cocaine's effects. Brain and body temperatures, as well as locomotion were measured simultaneously in rats during repeated, daily administration of cocaine (15 mg/kg i.p., daily for 5 days) under different experimental conditions. The drug was administered via (a). a chronically implanted catheter in quiet resting conditions, (b). an injection made under quiet rest or (c). an injection under activated conditions associated with placement in the cage. Although brain temperature and movement increased after cocaine administration in each condition, cocaine's action (evaluated as cocaine-saline difference for both parameters) was situational. Catheter-administered cocaine induced the strongest movement activation and robust, monophasic temperature increase, which remained relatively stable following each subsequent drug infusion. Cocaine injected during quiet and, especially, activated conditions, induced a weaker locomotor activation, while the temperature response (evaluated as drug-saline difference) had a biphasic pattern. Cocaine initially inhibited the temperature increases seen in saline-treated animals (0-20 min) and then induced a more prolonged hyperthermia, which was about twofold weaker than that seen after catheter-administered drug. Although movement activation gradually increased following repeated treatment in activated conditions, the magnitude of this sensitized motor response barely reached the levels induced by the initial cocaine administration via catheter. These data suggest that both the acute effects of cocaine in the brain and their change following repeated drug administration are dependent upon the ongoing neural activity state of the animal. Cocaine's interaction with this activity state is a crucial factor determining the behavioral effects of this drug, including state-dependent motor sensitization.     

Effects of para-chlorophenylalanine and 5-hydroxytryptophan on mouse killing behavior in killer rats.

The effects of para-chlorophenylalanine (PCPA) on mouse killing behavior were examined in natural killer rats. Forty-eight hr after injection, this serotonin synthesis inhibitor, at relatively low doses of 75 and 150 mg/kg, facilitated mouse killing, as indicated by a decrease in latency to attack the mouse. This effect was revealed in a test of satiation, in which five successive mice were presented to the rat, and also in a novel cage situation. Other than the shorter latencies to attack and kill mice, the killing response was similar in topography to the natural kill. The increase in killing after PCPA injection was associated with a reliable reduction in brain serotonin and in 5-hydroxyindoleacetic acid, and the time courses of the behavioral and biochemical changes were generally similar. In contrast to PCPA, injection of the serotonin precursor 5-hydroxytryptophan (5-HTP, 100 mg/kg) reliably lengthened attack and kill latencies in killer rats. In rats pretreated with PCPA, 5-HTP not only reversed this drug's facilitation of killing, but completely blocked killing in 67% of the rats tested. These results strengthen the hypothesis that brain serotonergic neurons are involved in the inhibition of mouse killing.     

Chronic ethanol tolerance as a result of free-choice drinking in alcohol-preferring rats of the WHP line

The development of tolerance to alcohol with chronic consumption is an important criterion for an animal model of alcoholism and may be an important component of the genetic predisposition to alcoholism. The aim of this study was to determine whether the selectively bred Warsaw High Preferring (WHP) line of alcohol-preferring rats would develop behavioral and metabolic tolerance during the free-choice drinking of ethanol. Chronic tolerance to ethanol-induced sedation was tested. The loss of righting reflex (LRR) paradigm was used to record sleep duration in WHP rats. Ethanol (EtOH)-naive WHP rats received a single intraperitoneal (i.p.) injection of 5.0 g ethanol/kg body weight (b.w.), and sleep duration was measured. Subsequently, rats had access to a 10% ethanol solution under a free-choice condition with water and food for 12 weeks. After 12 weeks of the free-choice intake of ethanol, the rats received another single i.p. injection of 5.0 g ethanol/kg b.w., and sleep duration was reassessed. The blood alcohol content (BAC) for each rat was determined after an i.p. injection of 5 g/kg of ethanol in naive rats and again after chronic alcohol drinking at the time of recovery of the righting reflex (RR). The results showed that the mean ethanol intake was 9.14 g/kg/24 h, and both sleep duration and BAC were decreased after chronic ethanol intake. In conclusion, WHP rats exposed to alcohol by free-choice drinking across 12 weeks exhibited increased alcohol elimination rates. Studies have demonstrated that WHP rats after chronic free-choice drinking (12 weeks) of alcohol develop metabolic tolerance. Behavioral tolerance to ethanol was demonstrated by reduced sleep duration, but this decrease in sleep duration was not significant.     

Acute increases by p-chlorophenylalanine of apomorphine-induced stereotyped behavior in the rat

The stereotyped behavioral syndrome induced in the rat by apomorphine was enhanced by acute systemic administration of PCPA. This effect was dependent on the dose of PCPA and half-maximal at approximately 150 mg/kg, i.p.; it occurred within 30 min, was greatest between 1 and 5 h and had nearly disappeared by 24 h after an acute dose of PCPA. A similar effect was not found at 24 or 48 h following 3 repeated doses of PCPA of 300 mg/kg/day. This effect of PCPA was not reversed by 5-HTP or by high doses of a decarboxylase inhibitor. PCPA alone did not produce stereotyped behavior, although it produced some behavioral excitation in high doses following inhibition of monoamine oxidase. This acute behavioral effect of PCPA to potentiate apomorphine-induced stereotyped responses is unexplained. It does not seem to be due to depletion of 5-HT or to the formation of an amine as an active metabolite. We suggest that PCPA can have behavioral excitatory actions independent of its 5-HT-depleting action.Abbreviations CNS (central nervous system) - Dopa (dihydroxyphenylalanine) - 5-HT (5-hydroxytryptamine, serotonin) - 5-HTP (l-5-hydroxytryptophan) - PCPA ([±]-p-chlorophenylalanine methyl ester·HCl) Supported in part by U.S. Public Health Service (NIMH) Grants MH-16674 and MH-25515, and Research Career Scientist Award MH-74370 (Dr. Baldessarini); and an award from the Scottish Rite Schizophrenia Research Foundation, Supreme Council 33°AA, Scottish Rite, Northern Masonic Jurisdiction of the U.S.A.     

5-HT_(1A)和5-HT_2受体功能与觉醒、睡眠成分关系的研究

目的　观察 5 HT1A受体激动剂 8 OH DPAT和HT2受体拮抗剂利坦色林 (ritanserin)对大鼠清醒和睡眠成分的影响 ,给予 5 HT1A受体激动剂和剥夺REM睡眠后皮层 5 HT2 受体结合能力的变化 ,进一步分析两种 5 HT受体亚型之间的关系以及 5 HT2 受体在睡眠中的作用。方法　利用大鼠睡眠自动分析系统定量分析清醒和睡眠成分的变化 ,注射PCPA制作剥夺睡眠的大鼠模型 ,水上平台法制作剥夺REM睡眠的大鼠模型 ,利用放射配体结合实验研究配体与受体结合力的变化。结果　 8 OH DPAT小剂量 (0 0 1mg·kg-1,sc)可以增加深睡眠和浅睡眠 ,减少觉醒 ;大剂量(0 375mg·kg-1,sc)则增加觉醒 ,减少全部睡眠成分。 5 HT2 受体拮抗剂ritanserin可以明显增加深睡眠 ,减少觉醒和REM睡眠。而 8 OH DPAT低剂量与ritanserin联合用药则使深浅睡眠明显增加 ,清醒和REM睡眠明显减少 ,具有协同作用。对于PCPA化使 3种睡眠成分均明显减少 ,觉醒比例明显增加的大鼠 ,ritanserin仅使浅睡眠增加其它成分不变。用 [3 H] ritanserin放射性配基结合显示 ,剥夺大鼠REM睡眠后皮层 5 HT2 受体Bmax值明显增加但Kd 值无变化 ;给予 5 HT1A激动剂 8 OH DPAT后皮层 5 HT2 受体Kd 和Bmax均降低。结论　 5 HT1A受体和 5 HT2 受体与睡眠有密切关系     

Developmental striatal critical period of activity-dependent plasticity is also a window of susceptibility for haloperidol induced adult motor alterations

Experience-dependent plasticity during critical periods of postnatal (PN) development shapes the adult brain anatomy and function. In rat motor system, there is a critical period of activity-dependent plasticity in the striatum (PN30-37). In this period, motor activity of running in a circular path induced in the Circling Training test (CT), elicits several plasticity changes on striatal synapses. It has been recently proposed that developmental critical periods might represent a unique pharmacological window of vulnerability to induce life-lasting behavioral modifications. In this paper we tested the hypothesis of existence of a pharmacological susceptibility to induce adult alterations on motor behavior during the striatal critical period. Due to its main action on the striatum and developmental motor behavioral effects, we applied the prototypical antipsychotic haloperidol to male rats (i.p. 0.7 or 2.5 mg/kg/day) before, during or after the period of plasticity (PN20-27, PN30-37 or PN40-47 respectively). Then, in the adulthood (PN80), we evaluated induced motor activity in the CT. The results showed that only rats exposed to the D2R blocker during the period PN30-37 increased the CT activity in comparison to control rats. Moreover, only these animals also showed an increase in the spontaneous locomotor activity at the open field test. These behavioral alterations were not accompanied by permanent striatal changes either on the number of D2R binding sites or on its mRNA expression levels. In conclusion, we have shown a pharmacological susceptibility of inducing adult motor behavior alterations by haloperidol during a natural critical period of activity-dependent plasticity (PN30-37) in rat striatum development. These results also emphasize the importance of behavioral screening for pharmacological agents to be used in developmental stages of maturation.     

Electromyographic power spectral changes associated with the sleep-awake cycle and with diazepam treatment in the rat

Power spectral analysis was used to study temporalis muscle EMG activities during the sleep-awake cycle in the rat. EMG spectra derived from EMG during the states of slow-wave sleep. REM sleep and wakefulness demonstrated qualitative and quantitative differences. Diazepam treatment produced reductions in EMG spectral power during wakefulness. Thus, our experimental model allows qualitative and quantitative delineation of EMG activity associated with behavioral changes or drug treatments.     

5-hydroxytryptamine depletion with para-chlorophenylalanine: effects on eating, drinking, irritability, muricide, and copulation.

Forty-four male rats were tested for eating, drinking, irritability, and copulation before and after intraperitonial para-chlorophenylalanine (PCPA) or control injections. Eleven of these rats were tested for muricide before and after PCPA injections (Group 1), while 18 others were tested only after PCPA injections (Groups 2). Group 1 rats received four 350 mg/kg PCPA injections spaced 6 days apart and showed hyperdipsia, weight loss, and a 24% increase in muricide. Group 2 rats received five daily 100 mg/kg PCPA injections repeated 11 days later and showed hyperdipsia and weight loss; in addition, 78% of them killed mice. Neither group showed significant changes in copulation. At the end of the experiment, t6 rats from Group 2 that were irritable and killed mice were injected intraperitonially with 5-hydroxytryptophan (80 mg/kg). Five of these rats lost their irritability and four stopped killing. The various behavioral changes were not corrleated significantly either with each other or with the degree of 5-hydroxytryptamine depletion. This tentatively suggests that PCPA may produce its effects on behavior by other means in addition to 5-hydroxytryptamine depletion.