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Rationale: Schizophrenic-spectrum patients commonly display deficits in preattentive information processing as evidenced, for example, by disrupted prepulse inhibition (PPI), a measure of sensorimotor gating. Similar disruptions in PPI can be induced in rodents and primates by the psychotomimetic drug phencyclidine (PCP), a noncompetitive inhibitor of the NMDA receptor. Mounting evidence suggests that the hunger hormone ghrelin and its constitutively active receptor influences neuronal circuits involved in the regulation of mood and cognition., Objectives: In the present series of experiments, we investigated the effects of ghrelin and the growth hormone secretagogue receptor (GHS-R1A) neutral antagonist, JMV 2959, on acoustic startle responses (ASR), PPI, and PCP-induced alterations in PPI., Results: Intraperitoneal (i.p.) administration of ghrelin (0.033, 0.1, and 0.33 mg/kg) did not alter the ASR or PPI in rats. Conversely, i.p. injection of JMV 2959 (1, 3, and 6 mg/kg), dose dependently decreased the ASR and increased PPI. Pretreatment with JMV 2959 at a dose with no effect on ASR or PPI per se, completely blocked PCP-induced (2 mg/kg) deficits in PPI while pretreatment with the highest dose of ghrelin did not potentiate or alter PPI responses of a sub-threshold dose of PCP (0.75 mg/kg)., Conclusion: These findings indicate that the GHS-R1A is involved in specific behavioral effects of PCP and may have relevance for patients with schizophrenia.

Aims: Out-of-hospital cardiac arrest is fatal without treatment, and time to defibrillation is an extremely important factor in relation to survival. We performed a cost-benefit analysis of dual dispatch defibrillation by ambulance and fire services in the County of Stockholm, Sweden., Methods and Results: A cost-benefit analysis was performed to evaluate the effects of dual dispatch defibrillation. The increased survival rates were estimated from a real-world implemented intervention, and the monetary value of a life ( 2.2 million) was applied to this benefit by using results from a recent stated-preference study. The estimated costs include defibrillators (including expendables/maintenance), training, hospitalisation/health care, fire service call-outs, overhead resources and the dispatch centre. The estimated number of additional saved lives was 16 per year, yielding a benefit-cost ratio of 36. The cost per quality-adjusted life years (QALY) was estimated to be 13,000, and the cost per saved life was 60,000., Conclusions: The intervention of dual dispatch defibrillation by ambulance and fire services in the County of Stockholm had positive economic effects. For the cost-benefit analysis, the return on investment was high and the cost-effectiveness showed levels below the threshold value for economic efficiency used in Sweden. The cost-utility analysis categorises the cost per QALY as medium.

Aichi virus (AiV), genus Kobuvirus, family Picornaviridae, is associated with gastroenteritis in humans. Previous studies have shown high seroprevalence but low incidence (0.9-4.1%) in clinical samples. We report here the first detection of AiV in Sweden. Two hundred twenty-one specimens from hospitalized patients with diarrhea, who were negative for other enteric viruses, were included in the study. AiV were detected in three specimens, all from elderly patients. Phylogenetic analysis revealed that the three Swedish isolates belonged to genotype A and were genetically closest to European and Asian strains of AiV.

Rationale: The cognitive and attentional deficits observed in schizophrenic patients are now considered central to the pathophysiology of the disorder. These deficits include an inability to filter sensory input as measured by, e.g., prepulse inhibition (PPI) reflex. Administration of phencyclidine (PCP), a drug that can induce a schizophrenia-like psychosis in humans, disrupts PPI in experimental animals. In rodents, this PCP-induced deficit can be blocked by pretreatment with nitric oxide (NO) synthase inhibitors. This suggests that some of the behavioral effects of PCP are mediated via NO. The substrate for in vivo NO production is L-arginine, and active transport of L-arginine via the cationic amino acid transporter may serve as a regulatory mechanism in NO production., Objectives: The aim of the present study was to study the effects of L-arginine transport inhibition, using acute and repeated L-lysine treatment, on PCP-induced disruption of PPI in mice., Results: Subchronic, and to some extent acute, pretreatment with L-lysine blocked a PCP-induced deficit in PPI without affecting basal PPI., Conclusions: L-lysine has been shown to block L-arginine transport in vitro, most likely via a competitive blockade and down regulation of cationic amino acid transporters. However, the importance of L-arginine transport as a regulatory mechanism in NO production in vivo is still not clear. The present results lend further support to the notion that some of the effects of PCP in the central nervous system are mediated via NO and that L-arginine transport may play a role in the regulation of NO production in the brain.

Rationale: The psychotomimetic drug, phencyclidine, induces schizophrenia-like behavioural changes in both humans and animals. Phencyclidine-induced disruption of sensory motor gating mechanisms, as assessed by prepulse inhibition of the acoustic startle, is widely used in research animals as a screening model for antipsychotic properties in general and may predict effects on negative and cognitive deficits in particular. Dopamine (DA) stabilizers comprise a new generation of antipsychotics characterized by a partial DA receptor agonist or antagonist action and have been suggested to have a more favourable clinical profile., Objective: The aim of the present study was to investigate the ability of first, second and third generation antipsychotics to interfere with the disruptive effect of phencyclidine on prepulse inhibition in mice., Results: Aripiprazole blocked the phencyclidine-induced disruption of prepulse inhibition. The atypical antipsychotic clozapine was less effective, whereas olanzapine, and the typical antipsychotic haloperidol, failed to alter the effects of phencyclidine on prepulse inhibition., Conclusions: The somewhat superior efficacy of clozapine compared to haloperidol may be explained by its lower affinity and faster dissociation rate for DA D2 receptors possibly combined with an interaction with other receptor systems. Aripiprazole was found to be more effective than clozapine or olanzapine, which may be explained by a partial agonist activity of aripiprazole at DA D2 receptors. In conclusion, the present findings suggest that partial DA agonism leading to DA stabilizing properties may have favourable effects on sensorimotor gating and thus tentatively on cognitive dysfunctions in schizophrenia.

Rationale: Schizophrenic patients show deficits in pre-attentive information processing as evidenced, for example, by disrupted prepulse inhibition, a measure of sensorimotor gating. A similar disruption can be observed in animals treated with the psychotomimetic agent, phencyclidine (PCP). However, the mechanism by which PCP alters brain function has not been fully elucidated. Recent studies have demonstrated that certain behavioural and neurochemical effects of PCP in rats and mice are blocked by nitric oxide (NO) synthase inhibition, suggesting an important role for NO in the effects of PCP., Objective: The aim of the present study was to investigate the effects of PCP on cAMP production in the ventral hippocampus and the role of NO in these effects using in vivo microdialysis in rats. Furthermore, the effects of PCP on acoustic startle reactivity and prepulse inhibition of acoustic startle were compared with changes in cAMP levels in the ventral hippocampus., Results: Significant increases in cAMP levels were observed in the ventral hippocampus following both local infusion (10(-4) mol/l and 10(-3) mol/l) and systemic administration (2 mg/kg) of PCP. The PCP-induced changes in prepulse inhibition and startle reactivity were associated in magnitude and duration with the increase in cAMP levels in the hippocampus. Furthermore, systemic administration of the NO synthase inhibitor, L: -NAME (10 mg/kg), blocked both the changes in cAMP levels and the behavioural responses induced by PCP., Conclusions: These findings indicate that the effects of PCP on prepulse inhibition and startle reactivity are associated with an increase in cAMP levels in the ventral hippocampus, and that this change in cAMP response may be linked to the production of NO.

Rationale: A deficit in attention and information processing has been considered a central feature in schizophrenia, which might lead to stimulus overload and cognitive fragmentation. It has been shown that patients with schizophrenia display a relative inability to gate incoming stimuli. Thus, patients repeatedly subjected to acoustic startle-eliciting stimuli habituate less to these stimuli than controls. Furthermore, schizophrenia-like symptoms can be induced by pharmacological manipulations in humans by psychotomimetic drugs, e.g. phencyclidine (PCP) and D-amphetamine (D-AMP). Recent studies show that the behavioural and biochemical effects of PCP in rodents are blocked by nitric oxide synthase (NOS) inhibitors, suggesting that NO plays an important role in at least the pharmacological effects of PCP., Objectives: The first aim of the present study was to investigate if PCP, MK-801 and D-AMP impair habituation of acoustic startle in mice. Secondly, we examine the effect of the NOS inhibitor, L-NAME, and the dopamine receptor antagonist, haloperidol, on drug-induced deficit in habituation., Results: PCP (4 mg/kg), MK-801 (0.4 mg/kg) and D-AMP (5.0 mg/kg), impaired habituation of the acoustic startle response in mice. This effect was reversed by the NOS inhibitor, L-NAME. The typical antipsychotic, haloperidol, reversed the effects of PCP and D-AMP, but not that of MK-801., Conclusions: The finding that PCP, MK-801 and D-AMP impair habituation in mice is consistent with the idea that these treatments model certain filter deficits seen in schizophrenic patients. Furthermore, the present results suggest that NO is critically involved in these effects on habituation, whereas that of dopamine is less clear.

Rationale: Schizophrenia is a major public health problem that affects approximately 1% of the population worldwide. Schizophrenia-like syndromes can be induced in humans by phencyclidine (PCP), a drug with marked psychomimetic properties. Recent studies show that the behavioural and biochemical effects of PCP in rats are blocked by nitric oxide synthase (NOS) inhibitors, suggesting that NO plays an important role in the pharmacological effects of PCP., Objective: The aim of this study was to investigate if PCP-induced disruption of prepulse inhibition of acoustic startle could be blocked by the NOS inhibitor, L-NAME, in mice., Results: The present study shows that PCP readily disrupts prepulse inhibition in mice normally without affecting pulse-alone trials. Furthermore, L-NAME blocked the PCP-induced disruption of prepulse inhibition in a dose-related manner., Conclusions: The PCP-induced disruption of prepulse inhibition and the ability of L-NAME to block this effect in both rats and mice suggest that this is a general and not a species-specific effect. The results of the present study further suggest that PCP exerts at least some of its actions in the central nervous system by a NO-dependent mechanism.

Rationale: Prepulse inhibition of acoustic startle is the reduction in startle response to an intense auditory stimulus when this stimulus is immediately preceded by a weaker prestimulus. Prepulse inhibition occurs normally in humans and experimental animals, but schizophrenic persons often exhibit a marked impairment in this measure. Previous studies have shown that dopamine (DA)-dependent neuronal mechanisms are involved in the modulation of prepulse inhibition., Objective: Experiments were conducted in rats to elucidate further the involvement of DA-ergic mechanisms in prepulse inhibition., Results: In line with previous studies, the indirect DA agonist, amphetamine, was shown to decrease prepulse inhibition. A close reverse relationship over time between DA overflow in the nucleus accumbens and prepulse inhibition was obtained using a technique allowing concomitant measurement of these parameters in awake, freely moving rats. This effect was more pronounced in amphetamine-treated rats compared to rats treated with equimolar doses of cocaine, which increased DA overflow without affecting prepulse inhibition. In other experiments, the combined treatment with subthreshold doses of the selective DA D1 agonist, SKF 38393, and the selective DA D2 agonist, quinpirole, was also shown to decrease prepulse inhibition. Finally, the selective DA D2 antagonist, raclopride, was shown to enhance prepulse inhibition., Conclusions: In line with previous studies, it is concluded that DA neurotransmission is involved in the modulation of prepulse inhibition and that the ventral part of the mesostriatal DA system may serve an important role in this modulation. Furthermore, the possibility is discussed that the discrepant results on prepulse inhibition obtained with amphetamine and cocaine may disclose functionally relevant differences in their mechanisms of action, and that the enhancement of prepulse inhibition induced by some antipsychotics in rats may reflect their propensity to induce adverse mental effects in humans.

Prepulse inhibition of acoustic startle is the normal reduction in startle response to an intense auditory stimulus when this stimulus is immediately preceded by a weaker prestimulus. Previous studies have shown that several neuroanatomical structures and pathways in the brain are involved in the modulation of prepulse inhibition. In the present study, the functional importance of the medial geniculate body (MG) in the modulation of prepulse inhibition was investigated. To this end, in vivo brain microdialysis probes were used to infuse drugs locally into the MG of awake, freely moving rats simultaneously with startle response and prepulse inhibition measurements in the same animals. Intrageniculate infusion of the sodium channel blocker, tetrodotoxin, significantly reduced prepulse inhibition without affecting baseline startle amplitude. A similar effect was obtained after intrageniculate infusion of the GABA(B) receptor agonist, baclofen. In addition, intrageniculate infusion of muscimol, an agonist at the GABA(A) receptor complex, reduced prepulse inhibition, although this effect was obtained at a higher concentration of the drug compared to that of baclofen. These studies suggest that the MG is involved in the modulation of prepulse inhibition and that auditory signals relayed via the MG may be subjected to inhibitory control at this level, involving GABA neurotransmission.

Male Sprague-Dawley rats were repeatedly treated with amphetamine (AMP, 1 mg/kg, SC) at 3- day intervals for 15 days and tested for prepulse inhibition of acoustic startle after each treatment. This treatment regimen induced sensitisation in the animals as evidenced by a progressive increase in the disruptive effect of AMP on prepulse inhibition. Persistent changes in brain function was indicated, since an increase in disruptive effect was observed in sensitised animals also after a 22-day-long drug- and test-free period. The development of sensitisation was blocked by pretreatment with haloperidol (HPD, 0.1 mg/kg, SC), which suggests that sensitisation to the disruptive effect of AMP was dependent on dopamine (DA) D2 receptor activation. Furthermore, the development of sensitisation was blocked by adrenalectomy, which suggests that sensitisation was dependent also on circulating adrenal hormones. Increased DA-ergic activity has been implicated in the pathophysiology of schizophrenia and AMP-induced sensitisation to the neuronal functions that modulate prepulse inhibition may be an experimental model to investigate this hypothesis.

The beta-adrenoceptor antagonist as well as serotonin 5-HT1 receptor antagonist, (-)alprenolol, was found to potentiate the disrupting effect of the noncompetitive NMDA receptor antagonist, dizocilpine, on prepulse inhibition (PPI) of the acoustic startle response (ASR) in the rat. The facilitating effect of dizocilpine on ASR amplitude was also potentiated by (-)alprenolol. (-)Alprenolol by itself did not affect either of these measures. These effects did not seem to be related to the unselective beta-adrenoceptor antagonist property of (-)alprenolol, since combined pretreatment with the beta1- and beta2-adrenoceptor antagonists, metoprolol and ICI 118551, did not alter the effects of dizocilpine on startle behaviour. However, a serotonergic influence was suggested by the fact that a facilitating effect of dizocilpine on ASR amplitude was also obtained by pretreatment with the 5-HT precursor, L-5-HTP, in benserazide-pretreated rats. Furthermore, pretreatment with the 5-HT2 selective receptor antagonist, MDL 100907, significantly reduced the (-)alprenolol-induced potentiation of the effects of dizocilpine on startle behaviour, while the 5-HT3 selective receptor antagonist, ondansetron, failed to do that. Finally, the (-)alprenolol-induced potentiation of the effects of dizocilpine was significantly reduced by pretreatment with the atypical antipsychotic, clozapine, and by the potential antipsychotic and selective dopamine D2 receptor antagonist, raclopride. This study suggests that altered 5-HT activity may influence the effects of psychotomimetic drugs such as dizocilpine on sensorimotor function, and this observation may have implications for the pharmacological treatment of schizophrenia in humans.

The ability of the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), to block the behavioural effects of the potent psychotomimetic, phencyclidine, was tested in rats using two different behavioural models. L-NAME was found to block both phencyclidine-induced disruption of prepulse inhibition of acoustic startle and phencyclidine-induced stimulation of locomotor activity. A selective action of L-NAME on the effects of phencyclidine was indicated, since L-NAME did not alter the effects of amphetamine, another potent psychotomimetic, in these behavioural models. These observations suggest that a nitric oxide-dependent mechanism may be involved in the effects of phencyclidine in the central nervous system.

Rotavirus is an important cause of gastroenteritis in young children. Locally produced antibodies in the intestinal mucosa are proposed to play an important role in the defence against rotavirus infection, but it is not established whether IgA alone can neutralize rotavirus, nor if IgA antibodies recognize epitopes involved in protective immunity. To evaluate whether human IgA plays a role in virus neutralization, serum IgA was purified from nineteen rotavirus seropositive individuals and examined for its neutralizing capacity by a peroxidase focus reduction test. In all nineteen sera IgA neutralizing antibodies against serotype 3 (rhesus rotavirus) were demonstrated. Purified IgA was further investigated and shown not only to neutralize rotavirus in solution but also to neutralize rotavirus already pre-bound to epithelial cells (MA-104). IgA epitope blocking assays with monoclonal antibodies directed against heterotypic epitopes on VP4 and VP7, revealed that IgA antibodies from 4/16 sera recognized epitopes on VP4, while 5/16 sera recognized a VP7 epitope. When whole sera were investigated for comparison 7 and 9/16 sera recognized epitopes on VP4 and VP7 respectively.

The effect of local injection of pertussis toxin (PTX) into the ventral tegmental area (VTA) on acoustic startle in rats was investigated. The PTX treatment caused only minor effects of its own on the acoustic startle response (ASR) or prepulse inhibition (PPI) of acoustic startle. However, systemic treatment with the indirect DA receptor agonist, amphetamine (2 mg/kg, SC) caused a significant increase in ASR magnitude and a significant disruption of PPI in PTX-treated rats while no such effects were observed in sham-treated rats. Treatment with the direct DA receptor agonist, apomorphine (2 mg/kg, SC), caused a significant disruption of PPI, an effect that was observed in both PTX- and sham-treated rats. Treatment with the 5-HT1A receptor agonist, 8-OH-DPAT (0.5 mg/kg, SC), did not affect PPI in either group but caused a marked increase in ASR magnitude in sham-treated rats. Interestingly, this effect was blocked in PTX-treated rats. The present results suggest that local injection of PTX into the VTA causes an increased sensitivity to the behavioural effects of psychostimulants on acoustic startle and may also suggest that intact midbrain 5-HT1A receptors are essential for the effect of 5-HT1A agonists on acoustic startle.

The action of the amantadine derivative memantine on the dopamine metabolism in the striatum and the n. accumbens of the rat was studied in vivo with different voltammetrical techniques. It was shown by differential pulse voltammetry that memantine enhanced extracellular levels of dopamine (DA) in the striatum of the anaesthetized rat, whereas an increase of 3,4 dihydroxyphenylacetic acid (DOPAC) could be observed only under freely moving conditions using square wave voltammetry. Under chloral hydrate anaesthesia the effect of memantine on extracellular DOPAC levels in the striatum and the n. accumbens was compared with MK-801, a well-known non-competitive NMDA-antagonist. Memantine did not affect striatal DOPAC concentrations under these conditions whereas MK-801 reduced the DOPAC signal. In the n. accumbens memantine enhanced the levels of extracellular DOPAC, while after MK-801 the signal was only slightly different from control. These findings suggest that in addition to its NMDA receptor antagonism, memantine affects dopaminergic transmission also by other mechanisms.

The effect of various typical (haloperidol) and atypical (clozapine, raclopride, remoxipride) antipsychotics on phencyclidine (PCP)-induced disruption of sensorimotor gating was tested in rats using an acoustic startle paradigm. Clozapine (4-40 mumol/kg), haloperidol (1-5 mumol/kg) and raclopride (1-12 mumol/kg) failed to reverse PCP-induced disruption of prepulse inhibition (PPI) of the acoustic startle response. In contrast, remoxipride (12-60 mumol/kg) caused a dose-dependent block of this effect. PCP-induced disruption of PPI is a widely accepted animal model of a corresponding behavioural deficit observed in schizophrenia although little evidence has been presented that it is in fact sensitive to antipsychotic agents. The present results indicate that remoxipride behaves in a unique way in this model compared to clozapine, haloperidol and raclopride.

A human IgA-radioimmunoprecipitation assay (IgA-RIPA) utilizing the galactose-binding lectin jacalin from the jack-fruit Artrocarpus integrifolia was developed. Among the human immunoglobulins, jacalin binds specifically to immunoglobulin A. The IgA-RIPA was used to characterize the serum IgA response to individual rotavirus polypeptides in nine paired sera from children (8-34 months of age) with an acute rotavirus infection. In acute sera the IgA response was mainly directed against the inner capsid proteins VP2 and VP6, with VP2 surprisingly being the most immunogenic protein while in the convalescent sera, the IgA response was directed not only against structural but also against non-structural proteins.

Polypeptide synthesis and morphogenesis of a group C rotavirus (AmC-1) adapted to a continuous swine testicular cell line was examined. SDS-PAGE analysis of 35S methionine labeled infected cell lysates revealed 9 viral polypeptides (122, 98, 79, 78, 43, 41, 35, 24, and 20 kD). Viral polypeptide synthesis appeared to be maximal at 7-10h post infection. Purified group C virus grown in the presence of trypsin was found to contain seven structural polypeptides (122, 98, 79, 53, 43, 41, and 30 kD) by protein blotting and five polypeptides (98, 79, 78, 43, and 41 kD) by immunoprecipitation with a hyperimmune rabbit antisera. Tunicamycin treatment, Concanavalin A binding, protein blotting, endo-H treatment and 2,6H-mannose labeling suggested that group C rotavirus contains one structural glycoprotein (41 kD) with a corresponding precursor mol. wt. of 37 kD and one not previously identified nonstructural glycoprotein (24 kD) with a corresponding precursor mol. wt. of < or = 20 kD. Electron microscopy of infected swine testicular cells revealed an assembly process for group C rotavirus similar to group A, with single-shelled particles budding through the rough endoplasmic reticulum with concomitant acquisition of a transient membrane.

A family outbreak of gastroenteritis caused by group C rotavirus is described. All five members of the family, with children between 8 and 15 years of age, fell ill with diarrhea. The diagnosis was initially based on the detection of rotavirus RNA showing a typical group C profile in gel electrophoresis in stool samples, and it was serologically verified from patient sera using a cell culture adapted porcine group C rotavirus as a source of standard antigen. All collected serum samples from the family contained IgM and/or IgG class antibodies to group C rotavirus measurable by immunofluorescence antibody test (IFAT). Group C rotavirus specific IgM class antibodies were present in the early serum samples in 3/4 patients. A roller tube neutralization test (NT) was established to demonstrate neutralizing antibodies to porcine group C rotavirus in human sera. These methods can be used to detect serologically group C rotavirus infections.

A porcine group C rotavirus (strain Cowden-AmC-1) was adapted and serially passaged in an established diploid swine testicular cell line (ST cells). Growth of group C rotavirus in ST cells, which in maintenance medium required trypsin, but not pancreatin resulted in cytopathic effect characterized by cellular stranding and subsequent cell lysis. Active replication and assembly were confirmed by RNA profile analysis, immune electron microscopy and immunofluorescence. Adaptation of non-group A rotavirus to a continuous cell line has not previously been reported and should facilitate progress in diagnostic procedures and vaccine development.

It is well known that benzodiazepines produce dependence in humans and locomotor stimulation in experimental animals. In this study the possible involvement of catecholamines in the diazepam-induced locomotor stimulation in mice were investigated. Diazepam was found to have a biphasic effect; increasing locomotor activity at a low dose (0.25 mg/kg), while decreasing it at higher doses (greater than 0.5 mg/kg). The locomotor stimulating effect of diazepam was effectively blocked by pretreatment with the benzodiazepine receptor antagonist flumazenil, as well as with the catecholamine synthesis inhibitor alpha-methyltryrosine and the dopamine receptor antagonists haloperidol, spiperone and SCH 23390. Taken together, these data indicate that the locomotor stimulating effect observed after low doses of diazepam is due to activation of brain dopaminergic systems involved in locomotor activity. The observations are discussed in relation to the hypothesis that dependence-producing drugs activate specific brain reward systems.

The effect of diazepam on spontaneous and tail-pinch-induced behaviour was monitored together with the measurement of extracellular ascorbate using constant potential voltammetry with carbon paste electrodes. Diazepam (3 mg/kg) was followed by eating during the 1st hour after administration in non-food-deprived rats and a reduction in the behaviour triggered by a mild tail-pinch 90 min after drug administration. There was no change in ascorbate concentration in parallel with the spontaneous eating; however, the brisk increase in ascorbate concentration in striatum, nucleus accumbens and hippocampus, which accompanies the tail-pinch, was decreased in size and duration after diazepam. This effect was blocked by the central benzodiazepine receptor antagonist Ro15 1788 (5 mg/kg).

The 5-hydroxytryptamine (5-HT) reuptake inhibitors zimelidine (10 mg/kg IP 1.5h pretest) or alaproclate (20 mg/kg IP 1.5h pretest) produced a prolongation of the ejaculation latency and of the post-ejaculatory interval in male rats treated with a subthreshold dose of 5-hydroxytryptophan (5-htp) (12.5 mg/kg IP 1h pretest). The 5-HTP-induced (50 mg/kg IP 1h pretest) prolongation of ejaculatory latency was effectively counteracted by administration of the 5-HT receptor blocking agent metergoline (1 mg/kg IP 1.5h pretest). All animals were treated with an inhibitor of peripheral aromatic amino acid decarboxylase, indicating that the effects are of central origin. The results support the contention that central 5-HT plays an inhibitory role in male rat sexual behavior.

Five ergot-related compounds were examined for their effects on the acoustic startle response in the rat. The startle amplitude and the startle latency were registered. 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT; 0.5-8 mg/kg) and lisuride (0.05-0.8 mg/kg) were found to enhance the startle amplitude, while the mainly DA receptor active ergot derivatives pergolide (0.2-0.8 mg/kg), bromocriptine (5-20 mg/kg) and LY 141865 (5-20 mg/kg) had no, or even the reverse, effect. All five compounds caused a prolongation of the startle latency. The increased startle amplitude caused by 8-OH-DPAT (2 mg/kg) and lisuride (0.2 mg/kg) was successfully antagonized by the 5-HT receptor antagonist methiothepin (0.1 mg/kg) but not by metergoline (1 mg/kg). 5-Hydroxy-L-tryptophan (L-5-HTP; 12.5-50 mg/kg), administered to pargyline- and benserazide-pretreated animals, was included for comparison. The serotonin precursor caused a marked increase in the startle amplitude and a shortening of the startle latency.

In the present series of experiments we have studied the effects of the dihydropyridine calcium channel antagonist nifedipine on ethanol-induced changes in behavior and dopamine (DA) release and metabolism. The locomotor-stimulatory effect of low doses of ethanol (2.5 g/kg) was antagonized by nifedipine, whereas ethanol-induced sedation observed after higher doses (4.5 g/kg) was potentiated. Biochemical studies indicated that ethanol enhanced the metabolism and release of DA in the striatum and the DA-rich limbic regions measured by post mortem analyses of DA-metabolites by HPLC with electrochemical detection and by in vivo voltammetry in anaesthetized rats, respectively. Pretreatment with nifedipine antagonized the stimulatory effects of ethanol on the DA-system. Nifedipine reduced the preference for ethanol, estimated by the relative intake of ethanol (6% v/v) and water in a free-choice situation, suggesting an influence of nifedipine not only on the stimulatory but also on the positive reinforcing effects of ethanol. The present results suggest that the locomotor-stimulatory and positive reinforcing effects of ethanol as well as its enhancing effect on dopaminergic activity may involve an enhancement of calcium mediated mechanisms.

Two 2-(di-n-propylamino)tetralin (DPAT) compounds, 8-OH-DPAT and 5-OH-DPAT, with reported effects on central 5-HT and DA receptors respectively, were tested for their effects on the acoustic startle response in rats. 8-OH-DPAT was given in doses of 0.25-2.0 mg/kg IP and 5-OH-DPAT in doses of 1.0-8.0 mg/kg IP. Both compounds increased the startle response significantly in a dose-dependent manner, but 8-OH-DPAT appeared to be about 30 times as potent and to have a higher efficacy than 5-OH-DPAT. In addition, the effects on the startle response of L-5-HTP, 25-100 mg/kg IP, and L-dopa, 25-100 mg/kg IP, administration to animals pretreated with the inhibitor of aromatic L-amino acid decarboxylase, benserazide (25 mg/kg IP) were included for comparison. A small, but significant increase in the startle amplitude was found after the highest dose of L-5-HTP, whereas no effects were observed after L-dopa administration.