Increase In Serotonergic Activity Research Articles

A case report of suspected serotonin syndrome following administration of fentanyl

Background: Serotonin syndrome (SS) is a potentially life-threatening drug-induced toxidrome that can occur because of an overdose of a serotoninergic drug or the combination of multiple drugs with serotoninergic activity at therapeutic doses, leading to an increase in serotonergic activity in the central and peripheral nervous system. SS in the setting of general anesthesia is uncommon but possibly underdiagnosed because of the variability in its severity and symptomatology. This report presents a case of severe SS following the administration of fentanyl during induction of general anesthesia. Additionally, it provides a brief overview of the pathophysiology, clinical features, management strategies, and commonly used drugs by anesthesiologists that can potentially result in a fatal interaction.

Serotonin Syndrome: The Role of Pharmacology in Understanding Its Occurrence.

Serotonin syndrome (SS) is a potentially fatal adverse drug reaction characterized by an exaggerated increase in serotonergic activity in the central and peripheral nervous systems. It presents a constellation of signs and symptoms related to behavioral changes, neuromuscular excitability, and autonomic instability. These symptoms can occur in both mild and severe forms. SS can be triggered by the therapeutic use of a drug that increases serotonin (5-HT) availability in the synaptic cleft or by the co-administration of two or more drugs that provide this increase. With the escalating use of antidepressants by the world's population, this adverse reaction may be more recurrent. However, SS is often overlooked by patients or not diagnosed by doctors. This review aims to improve awareness about SS and provide a pharmacological perspective to explain its occurrence. Evidence shows that other neurotransmitters may also be involved with the pathology of SS. Furthermore, SS and neuroleptic malignant syndrome (NMS) seem to be part of the same pathological spectrum, especially in atypical NMS cases. The emergence of the syndrome's symptoms may be closely related to pharmacokinetic and/or pharmacodynamic polymorphisms that lead to an increase in the 5-HT available to or 5-HT signaling by specific receptors, thus constituting an important area for future investigations.

Ant1 mutant mice bridge the mitochondrial and serotonergic dysfunctions in bipolar disorder

Although mitochondrial and serotonergic dysfunctions have been implicated in the etiology of bipolar disorder (BD), the relationship between these unrelated pathways has not been elucidated. A family of BD and chronic progressive external ophthalmoplegia (CPEO) caused by a mutation of the mitochondrial adenine nucleotide translocator 1 (ANT1, SLC25A4) implicated that ANT1 mutations confer a risk of BD. Here, we sequenced ANT1 in 324 probands of NIMH bipolar disorder pedigrees and identified two BD patients carrying heterozygous loss-of-function mutations. Behavioral analysis of brain specific Ant1 heterozygous conditional knockout (cKO) mice using lntelliCage showed a selective diminution in delay discounting. Delay discounting is the choice of smaller but immediate reward than larger but delayed reward and an index of impulsivity. Diminution of delay discounting suggests an increase in serotonergic activity. This finding was replicated by a 5-choice serial reaction time test. An anatomical screen showed accumulation of COX (cytochrome c oxidase) negative cells in dorsal raphe. Dorsal raphe neurons in the heterozygous cKO showed hyperexcitability, along with enhanced serotonin turnover in the nucleus accumbens and upregulation of Maob in dorsal raphe. These findings altogether suggest that mitochondrial dysfunction as the genetic risk of BD may cause vulnerability to BD by altering serotonergic neurotransmission.

Increased reactivity and monoamine dysregulation following stress in triploid Atlantic salmon (Salmo salar)

Artificial triploid salmonids are sterile and therefore commercially bred to prevent genetic interactions between wild and domestic fish strains. The full biological effects of having an extra chromosome set are largely unknown, but triploids are considered to be more sensitive to sub-optimal environmental conditions and to be stressed by the presence of diploid conspecifics. Brain serotonergic and dopaminergic activity are known to regulate the stress response in vertebrates, but monoamine systems in diploid and triploid fish have yet to be compared. Here we study monoamine neurochemistry in the telencephalon and brain stem of juvenile diploid and triploid Atlantic salmon (Salmo salar) in response to stress (unstressed vs stressed individuals) and holding (separate- vs mixed-ploidy) conditions. Both diploids and triploids showed an increase in serotonergic activity following stress, but the increase was significantly greater in the telencephalon of triploids compared to diploids. Furthermore, while telencephalic dopaminergic activity was significantly increased in diploids following stress, there was no response in triploids. Holding conditions had a significant effect on dopaminergic activity in the brain stem of diploids only, with lower values in mixed- compared to separate-ploidy conditions. These results suggest artificially produced triploids experience increased reactivity and monoaminergic dysregulation following stress that may impede their welfare and performance.

The response of brain serotonergic and dopaminergic systems to an acute stressor in rainbow trout: a time-course study

The brain monoaminergic neurotransmitter systems are known to be involved in the integrated response to stress in vertebrates. However, present knowledge about the timing of their actions as well as their specific roles in the regulation of the endocrine axes that drive the stress response is incomplete. This is partly because of the complexity of the reciprocal interactions among the monoaminergic systems and other biochemical effectors of the stress response such as corticotropin-releasing factor (CRF), arginine vasotocin (AVT), adrenocorticotropic hormone (ACTH) and corticosteroids. In this study, we show for the first time in teleost fish (rainbow trout) the short- and mid-term time course of the response of the forebrain serotonergic and dopaminergic activities after exposure to an acute stressor. Other stress markers like the plasma levels of cortisol, glucose and lactate were also monitored, providing a context in which to precisely locate the monoaminergic activation within the fish acute stress response. Our results show that acute stress induced a rapid increase in forebrain serotonergic activity, which became elevated after only 15 s of chasing. Several hours after stress, serotonergic activity recovered its basal levels, in parallel with the recovery of other stress markers such as plasma catecholamines and cortisol. Dopaminergic activity was also increased after stress, but only in the telencephalon and only after 20 min. The increase in serotonergic activity happened before the elevation of plasma catecholamines, suggesting that this monoamine system could have a key role in triggering the initial steps of the activation of not only the hypothalamus-pituitary-inter-renal axis but also the brain-sympathetic-chromaffin axis in fish.

The Selective Serotonin Reuptake Inhibitor Paroxetine Decreases Breakpoint of Rats Engaging in a Progressive Ratio Licking Task for Sucrose and Quinine Solutions

Increased serotonergic activity has been shown to reduce motivation to ingest, which may involve, in part, gustatory processes. Here, we examined the effect of paroxetine, a selective serotonin reuptake inhibitor, on appetitive responding for a preferred and an avoided taste solution using a progressive ratio (PR) task in which licking was employed as the operant. Male Sprague-Dawley rats (n = 8/taste stimulus) were trained to respond for a concentration series of sucrose or quinine on fixed and PR schedules of reinforcement. Performance for sucrose was assessed while the rats were partially food- and water-restricted and nondeprived, and performance for water and quinine was assessed while the rats were water-deprived. Then, the rats were injected with vehicle (10% dimethyl sulfoxide, 1mL/kg intraperitoneal [ip], -1h) or paroxetine (5mg/kg), and their responding on a PR schedule for sucrose measured when the rats were nondeprived or for water and quinine when the rats were water-deprived. Paroxetine decreased breakpoint, which was defined as the number of operant (e.g., dry) licks in the final reinforced ratio, for water, quinine, and sucrose. This demonstrates that a general systemic increase in serotonergic activity decreases the appetitive-based responses to both preferred and nonpreferred fluids under different deprivation states.

Vilazodone approved for major depression

Clinical Data Inc. of Newton, Massachusetts, on January 24 announced the approval of vilazodone hydrochloride oral tablets for the treatment of adults with major depressive disorder. The drug will be marketed as Viibryd by Clinical Data subsidiary Trovis Pharmaceuticals, formerly known as PGxHealth, and will be available during the second quarter of this year. According to the FDA-approved labeling for vilazodone, the drug is a selective serotonin reuptake inhibitor and serotonin type 1A-receptor partial agonist. The labeling states that vilazodone’s mechanism of action is unknown but may result from an increase in serotonergic activity in the central nervous system. Labeling for vilazodone includes a boxed warning and medication guide that describe an increased risk of suicidal thinking in children, adolescents, and young adults who use antidepressants. The warning emphasizes that vilazodone is not indicated for pediatric use. The drug is contraindicated in patients who take monoamine oxidase inhibitors (MAOIs) and should not be taken within 14 days of starting or stopping an MAOI. Concomitant treatment with vilazodone and an MAOI may increase the risk of serotonin syndrome, according to vilazodone’s labeling.

Interleukin‐1β and Insulin Elicit Different Neuroendocrine Responses to Hypoglycemia

Interleukin (IL)-1beta induces a prolonged hypoglycemia in mice that is not caused by a reduction in food intake and is dissociable from insulin effects. There is a peripheral component in the hypoglycemia that the cytokine induces resulting from an increased glucose uptake, an effect that can be exerted in a paracrine fashion at the site where IL-1 is locally produced. However, the maintenance of hypoglycemia is controlled at brain levels because the blockade of IL-1 receptors in the central nervous system inhibits this effect to a large extent. Furthermore, there is evidence that the cytokine interferes with counter regulation to hypoglycemia. Here we report that administration of IL-1 or long-lasting insulin results in different changes in food intake and in neuroendocrine mechanisms 8 h following induction of the same degree of hypoglycemia (40-45% decrease in glucose blood levels). Insulin, but not IL-1, caused an increase in food intake and an endocrine response that tends to reestablish euglycemia. Conversely, a decrease in noradrenergic and an increase in serotonergic activity in the hypothalamus occur in parallel with a reduction of glucose blood levels only in IL-1-treated mice, effects that can contribute to the maintenance of hypoglycemia. These results are compatible with the proposal that IL-1 acting in the brain can reset glucose homeostasis at a lower level. The biologic significance of this effect is discussed.

The effects of increased serotonergic activity on human sensory gating and its neural generators

Schizophrenia is a disabling illness with deficits in core mental functions such as sensory gating. The P50 amplitude is an (usually auditory) evoked brain potential that, in a so-called double-click paradigm, can be used to quantify sensory gating. Reports on serotonergic modulation of P50 suppression are sparse. The objective of this study was to study the effects of increased serotonergic activity on parameters of P50 suppression in healthy volunteers. In a double-blind placebo-controlled crossover design, 21 healthy male volunteers received either placebo or a dose of 10 mg of escitalopram (selective serotonin reuptake inhibitor), after which they were tested in a P50 suppression paradigm. Furthermore, an attempt was made to identify the neural generators of the P50 evoked potential. Escitalopram did not affect P50 suppression but was found to increase P50 amplitude to the first (or conditioning) stimulus. Two bilateral sources located in the temporal cortex, two bilaterally located near the eyes, and one in a fronto-central location were identified, the latter correlating positively with the P50 amplitude. In the current study, escitalopram did not affect P50 suppression in healthy male volunteers, which indicates that sensory gating is not affected by a nonspecific increase in serotonergic activity. Furthermore, a generator with a fronto-central location in the brain (possibly the anterior cingulate) was found to be the primary source of the P50 evoked potential.

Appetite-suppressing effects of ammonia exposure in rainbow trout associated with regional and temporal activation of brain monoaminergic and CRF systems

To assess whether the brain's monoaminergic and/or corticotropin-releasing factor (CRF) systems may be involved in mediating the appetite-suppressing effects of high environmental ammonia levels, we exposed rainbow trout to one of four NH4Cl treatments (0, 500, 750, 1000 micromol l(-1)) for 24 or 96 h and monitored changes in food intake, brain serotonin (5-HT) and dopamine (DA) activity, CRF and urotensin I (UI) mRNA levels, and plasma cortisol levels. Food intake decreased in a dose-dependent manner after 24 h of ammonia exposure and partially recovered in all groups after 96 h. Ammonia also elicited dose-dependent increases in serotonergic activity in the hypothalamus (HYP), telencephalon (TEL) and posterior brain (PB). Whereas the increase in serotonergic activity was timed with the 24 h food intake inhibition, TEL and PB serotonergic activity increased after 96 h. In the PB, exogenous ammonia also elicited dose-dependent increases in dopaminergic activity after both 24 and 96 h of exposure. Transient increases in TEL CRF and UI mRNA levels, HYP UI mRNA levels, and plasma cortisol concentrations were evidence that the hypothalamic-pituitary-interrenal (HPI) stress axis was primarily stimulated in the first 24 h of ammonia exposure when food intake was depressed. Overall, the transient nature of the appetite suppression during chronic ammonia exposure, and the time-dependent changes in brain monoaminergic and CRF systems, implicate 5-HT, DA, CRF and UI as potential mediators of the appetite-suppressing effects of ammonia. Among these anorexigenic signals, our results specifically identify hypothalamic 5-HT as a potentially key neurobiological substrate for the regulation of food intake during exposure to high external ammonia concentrations.

Sex differences in behavioral, neurochemical and neuroendocrine effects induced by the forced swim test in rats

The forced swim test (FST) has been considered as a pharmacologically valid test of the depressive syndrome in rodents. However, few studies have focused on neurochemical and behavioral responses during FST in both male and female rats. Thus, we investigated certain behavioral and neuroendocrine responses as well as the serotonergic activity after the application of FST in both sexes. Our data show that the duration of immobility was increased in both male and female rats during the 2nd session of the FST. Sex differences are observed in some behavioral responses, such as head swinging that is mostly present in male rats. In female rats FST induced a decrease in serotonergic activity in hippocampus and hypothalamus while in male rats it induced an increase in serotonergic activity in hypothalamus. Corticosterone serum levels were elevated in both sexes. However, hippocampal GR mRNA levels tended to be increased in males and females respectively. Moreover, hypothalamic serotonin (5-HT) 1A mRNA levels were decreased in female rats while in male rats hippocampal 5-HT 1A mRNA levels were increased. These data have shown that FST induces “depressive like symptoms” in both sexes and provide evidence that sex differences characterize certain behavioral aspects in the FST. Notably, hippocampal and hypothalamic serotonergic activity has been differentially modified in male rats compared with female rats and these neurochemical findings could be relevant to the differentiated expression of 5-HT 1A receptor. Hypothalamic–pituitary–adrenal axis activity was also affected by FST application in a sex specific manner. The present results support that FST induced behavioral, neurochemical and neurobiological alterations, which are sex dependent.

NOT ENOUGH MALES? MONOAMINES CHANGE EVERYTHING!

The saddleback wrasse, Thalassoma duperrey, inhabits corals reefs in the Hawaiian Islands. Remarkably, when the ratio of males to females in a population of wrasse becomes too low, the largest female transforms herself into a male over a 6–8-week period. Unsurprisingly, sex reversal in fishes requires a complete reorganization of physical, physiological and behavioural systems. In addition, sex reversal requires the conversion of external social cues into internal chemical cues. While past studies had investigated the roles of various hormones, neurotransmitters and neuromodulators as the trigger for the sex reversal process, an important group of chemicals that had not yet been investigated were the monoamine neurotransmitters such as dopamine, serotonin and noradrenaline. The hypothesis of the study by Larson and coworkers was that sex reversal in the wrasse would be accompanied by changes in the activities of these monoamines within different brain regions.In order to induce sex reversal in the larger fish and investigate the role of monoamines in the process, a series of floating enclosures were set up and a large and small female were placed in each. The team chose to monitor regions of the brain that are known to be involved in regulating sexual function and behaviour and are homologous to mammalian systems. The team sampled brains from the larger fish at various time points throughout the process of sex reversal and measured the monoamine levels using high-performance liquid chromatography (HPLC).Larson and colleagues found changes in monoamine metabolism in all of the brain regions that were examined. The most prevalent alterations in monoamine system activation were observed during the first week of sex reversal, at which time the sexual transition is primarily behavioural.One of the brain regions sampled appeared to be involved in regulating the fish's physical alterations. In the preoptic area of the brain, linked with male sexual function and behaviour in all vertebrates, the team found changes in both serotonergic activity and noradrenergic activity, which could potentially trigger the reorganization of the reproductive axis.The remaining four regions of the brain appeared to be involved in altering the female's behaviour during her sexual transition. The amygdala, an area in the brain that is important with respect to aggression, dominance and stress in vertebrates, exhibited significant changes in serotonin metabolism during sex reversal in wrasse. These changes were probably related to the observable increase in territorial acquisition and defense as the wrasse changed from female to male. In the ventral hypothalamus, noradrenergic activity, which is typically associated with female behaviour in this region of the brain, was reduced. By contrast, the locus coeruleus showed an increase in noradrenergic activity in the later stages of sex reversal, probably in response to an increase in circulating male sex hormones such as testosterone. The raphe nucleus showed an increase in serotonergic activity at the early, behavioural stages of sex reversal. During this time it is critical for the changing female to show dominance over other females, and dominant behaviour results in lower serotonergic activity in many animal models.The present study is the first to investigate monoamines and their role in environmentally stimulated sex reversal and has revealed that monoamines in different brain regions are important in both behavioural and gonadal sex reversal in the saddleback wrasse.

Monoaminergic changes associated with socially induced sex reversal in the saddleback wrasse

The process of sex reversal in fishes is socially mediated and requires a total reorganization of the hypothalamo–pituitary–gonadal axis. When the ratio of males to females in a population of saddleback wrasse ( Thalassoma dupperrey) is too low, the largest female becomes male over the course of 6 to 8 weeks. This event requires the conversion of external social cues into internal chemical cues. In an attempt to investigate the role monoamines might play in this process, two females were housed together in floating enclosures in order to induce sex reversal in the larger. Brains were sampled at various time points throughout the process of sex reversal. Monoamines were measured in the amygdala, preoptic area, ventral hypothalamus, locus coeruleus and raphe nucleus. Changes were demonstrated in monoamine metabolism for all brain regions examined. The most important changes in monoamine-system activation were seen during the first week of sex reversal. It is during this time that transitional animals undergo behavioral sex reversal. There is an increase in serotonergic activity in the amygdala which is likely related to territorial acquisition. The absence of male aggression results in a less stressful environment for the female and a reduction in serotonergic activity in the preoptic area allowing for an increase in noradrenergic activity potentially triggering the reorganization of the reproductive axis. In the ventral hypothalamus, there is a decrease in noradrenergic and increase in dopaminergic activity associated with this change from female to male. The locus coeruleus shows an increase in noradrenergic activity later in the process of sex reversal which is probably a response to more circulating androgens. In the raphe nucleus, there is a decrease in serotonergic activity at the time of behavioral sex reversal. This decrease in serotonergic activity is linked to the behavioral component of sex reversal. This study suggests that monoamines play a very important role in both behavioral and gonadal sex reversal in the saddleback wrasse, the former under the control of serotonin in the raphe and the latter mediated via serotonergic effects on norepinephrine in the preoptic area.

Biphasic effects of pu-chung-i-chi-tang on sedation and excitation.

The biphasic effects of Pu-Chung-I-Chi-Tang (PCT) on sedation and excitation in acute treatment or after one-week consecutive treatment were studied. The results indicated that PCT produces sedation in acute treatment and excitation after one-week consecutive treatment. The sedative mechanism of PCT in acute treatment might be due to an increase in serotonergic activity and a decrease in dopaminergic activity. However, the excitatory mechanism of PCT after one-week consecutive treatment might involve the increase in dopaminergic activity and the decrease in serotonergic activity.

Serotonergic mechanisms involved in the exploratory behaviour of mice in a fully automated two-compartment black and white text box.

A fully automated version of the black and white two-compartment box for mice is presented. The anxiolytic-like effects of the benzodiazepines, diazepam and chlordiazepoxide, were confirmed, and the involvement of serotonergic mechanisms was studied in this animal model of anxiety. The partial 5-HT1A receptor agonists, buspirone and ipsapirone showed anxiolytic-like effects in a limited dose interval. The full agonist hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) was inactive. The non-selective 5-HT1 receptor agonist, eltoprazine, induced marked increases of exploratory behaviour in the white compartment over a broad range of doses. Also pindolol a mixed 5-HT1A/1B and beta-adrenergic receptor antagonist showed anxiolytic-like effects, whereas another compound with a similar profile (-)-, penbutolol and the beta-adrenoceptor antagonist ICI 118,551, was inactive. The 5-HT2A/2C receptor antagonist, ritanserin, showed anxiogenic-like, and the 5-HT3 receptor antagonists, zacopride and ondansetron, showed anixiolytic-like effects. An overall increase of serotonergic activity by means of 5-HT uptake inhibition (citalopram), 5-HT release (fenfluramine) or administration of a 5-HT precursor (1-5-HTP) facilitated exploratory activity in the white compartment. Reduction of serotonergic activity by treatment with the 5-HT depletor p-chloro-phenylalanine methyl ester (PCPA) did not change the exploratory behaviour, but attenuated the response to fenfluramine significantly.

Roles of brain monoamine neurotransmitters in agonistic behaviour and stress reactions, with particular reference to fish

Abstract 1. Experimental results on the involvement of brain monoamines in agonistic behaviour and stress in fish are reviewed and discussed in relation to available data from other vertebrates. 2. In fish as well as mammals, stress induces increased brain serotonergic activity, and a similar increase in serotonergic activity is seen in subordinate individuals in a dominance hierarchy. 3. The brain serotonergic system appears to inhibit aggression and spontaneous locomotor activity in both fish and mammals. 4. Subordinate fish show several behavioural characteristics, notably inhibition of aggressive behaviour, low spontaneous locomotor activity and decreased food intake, that are likely to be related to their increased brain serotonergic activity. 5. By contrast, the brain dopaminergic system appears to stimulate aggressive behaviour in both fish and mammals, and dominant fish show signs of elevated dopaminergic activity in telencephalon. 6. The similarities between fish and mammalian monoaminergic functions suggest that these are phylogenetically very old mechanisms that have been conserved during the last 400 million years of vertebrate evolution.

Spontaneous Locomotor Activity in Arctic Charr Measured by a Computerized Imaging Technique: Role of Brain Serotonergic Activity

ABSTRACT Using a computerized video-image analysis system, spontaneous locomotor activity was measured in dominant and subordinate individuals of Arctic charr (Salvelinus alpinus) and in individuals treated with inhibitors of serotonin (5-HT) synthesis and re-uptake. Arctic charr were put together in pairs. After 1 week, subordinate individuals were found to have elevated brain levels of 5-hydroxyindoleacetic acid, a major 5-HT metabolite, suggesting an increase in serotonergic activity. The subordinate individuals had significantly lower spontaneous locomotor activity than the dominant fish. Similarly, Arctic charr displayed a significantly reduced locomotor activity when their serotonergic activity was stimulated by the specific 5-HT re-uptake inhibitor zimeldine. In contrast, fish treated with the 5-HT synthesis inhibitor p-chlorophenylalanine showed a significant increase in locomotor activity. Dominant, subordinate and pharmacologically treated fish all had very similar activity rhythms for the 18h test period. Thus, neither the previous social experience nor the pharmacological treatment seemed to affect the diurnal activity rhythm per se. Taken together, these results suggest that the brain serotonergic system inhibits locomotor activity and support the possibility that 5-HT is involved in the inhibition of locomotor activity displayed by subordinate fish.

Influence of modified casomorphins on yawning behavior of rats

Apomorphine-induced yawning was completely suppressed in animals treated with 5 nmol [D-Pro 4]casomorphin (CM) (ICV), 10 nmol [D-Phe 3]CM (ICV) or 10 nmol [D-Pip 4]CM (ICV). The apomorphine-induced yawning was also decreased, by des-Tyr analogs, but only by about 50%. Physostigmine (0.15 mg/kg, IP) induced yawning. The physostigmine-induced yawning was suppressed by 5 nmol [D-Pro 4]CM and 10 nmol [D-Phe 3]CM. Both [des-Tyr-D-Phe 3]CM and [des-Tyr-D-Pip 4]CM were without effect, whereas [des-Tyr-D-Pro 4]CM increased significantly the physostigmine-induced yawning. The results suggest that dopaminergic transmission can be modulated by β-casomorphin derivatives, thus resulting in a decrease in yawning. In the case of the des-tyrosine derivatives, we can assume a dopaminergic modulation, too. An increase in serotonergic activity might be supposed for [des-Tyr-D-Pro 4]CM.

Effects of Season, Pinealectomy, and Blinding, Alone and in Combination, on Hypothalamic Monoaminergic Activity in the Teleost Channa punctatus (Bloch)

In Channa punctatus, day-night variations in hypothalamic 5-HT (serotonin) and monoamine oxidase (MAO) activity were noticed in preparatory but not other phases (prespawning and postspawning) of the annual reproductive cycle. Hypothalamic MAO, 5-HT, and norepinephrine (NE) activity was found to be high in the prespawning phase and low in the postspawning phase. Dopamine (DA) activity, on the other hand, was high in the postspawning season and low in the prespawning phase. Pinealectomy caused season-dependent effects on hypothalamic monoaminergic activity, with a significant increase in serotonergic activity and a significant reduction in MAO activity at midscotophase during the preparatory phase (March) but not in the prespawning (May-June) or postspawning (September) phases. Hypothalamic catecholaminergic (CA) activity was not influenced by pinealectomy during any of the seasons. To determine whether or not the photoperiodic influences on daily variations of 5-HT and MAO in the preparatory phase are mediated via pineal and/or lateral eyes, fish were pinealectomized and/or blinded in January, when there is no rhythm, and sacrificed in February, when a day-night variation normally sets in. The day-night difference in 5-HT content and activity and MAO activity was not abolished by pinealectomy or blinding alone; but the combination (pinealectomy + blinding) obliterated the daily variation only in 5-HT content and in MAO activity. However, pinealectomy and blinding, alone or in combination, caused a significant elevation of 5-HT activity (not its level) and a significant decrease in MAO activity at midscotophase, with the combination having an additive effect. Hypothalamic CA content or activity was not affected by these regimes. The results show that photoperiodic influence on the daily pattern of 5-HT and MAO activity is mediated through and by the interaction of the pineal and lateral eyes.

Manufacture and use of fused silica cannulas for intracerebral injections in freely moving rats

This report describes in detail the assembly and use of miniature cannulas for intracerebral injections in freely moving rats. Guide and injection cannulas were prepared from polyimid-coated fused silica capillaries as routinely in use for gas chromatography, in this way avoiding the permanent contact of stainless-steel with brain tissue. The outer diameter of the guide capillary measured 300 μm. that of the injection capillary 170 μm. In spite of their fragile appearance, the capillaries were robust and easy to handle. In the same animal, up to 20 consecutive injections were possible. In the course of 2 years 204 cannulas directed to the amygdala or the lateral ventricle were implanted, and only in 8 rats (4%) the inner capillary broke and plugged the guide cannula, making injections impossible. Histological examination of brains implanted for up to 2 months demonstrated only blunt scar formation along the cannula's track. No changes in transmitter levels (biogenic amines, amino acids) could be detected in chronically implanted rat brains except for a slight increase in serotonergic activity in the contralateral piriform cortex. Intra-amygdaloid injection of 0.32 μl 0.9% saline resulted in a mild and transient reduction of GABA levels in both piriform cortices, without any detectable persistent histopathological consequences.