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PubMed2006

In utero exposure to nicotine and chlorpyrifos alone, and in combination produces persistent sensorimotor deficits and Purkinje neuron loss in the cerebellum of adult offspring rats.

This study was carried out to investigate the effect of in utero exposure to the cholinotoxicants, nicotine and chlorpyrifos, alone or in combination on neurobehavioral alterations and neuronal morphology latter in adult age. In the present study, 90 days old (corresponding to a human adult age) male and female offspring rats were evaluated for neurobehavioral, and neuropathological alterations following maternal, gestational exposure to nicotine and chlorpyrifos (O,O-diethyl-O-3,5,6-trichloro-2-pyridinyl phosphorothioate), alone and in combination. Female Sprague-Dawley rats (300-350 g) with timed-pregnancy were treated with nicotine (3.3 mg/kg/day, in bacteriostatic water via s.c. implantation of mini osmotic pump), chlorpyrifos (1.0 mg/kg, daily, dermal, in 75% ethanol, 1.0 ml/kg) or a combination of both chemicals, on gestational days (GD) 4-20. Control animals received bacteriostatic water via s.c. implantation of mini osmotic pump and dermal application of 70% ethanol. The offspring at postnatal day (PND) 90 were evaluated for neurobehavioral performance, changes in the activity of plasma butyrylcholinesterase (BChE) and acetylcholinesterase (AChE), and neuropathological alterations in the brain. Neurobehavioral evaluations included beam-walk score, beam-walk time, incline plane performance and forepaw grip time. Male and female offspring from mothers treated with nicotine and CPF, alone or in combination showed impairments in the performance of neurobehavioral tests, indicating sensorimotor deficits. Female offspring from mothers treated with a combination of nicotine and chlorpyrifos showed significant increase in plasma BChE activity. Brain regional AChE activity showed differential increases in male and female offspring. Brainstem and cerebellum of female offspring from mothers treated with nicotine or chlorpyrifos, alone or in combination showed increased AChE activity, whereas brainstem of male offspring from mothers treated with nicotine alone or a combination of nicotine and chlorpyrifos showed increase in AChE activity. Also, male offspring exposed in utero to nicotine exhibited increased AChE activity. Histopathological evaluations using cresyl violet staining showed a decrease in surviving Purkinje neurons in the cerebellum in offspring of all treatments groups. An increase in glial fibrillary acidic protein (GFAP) immuno-staining was observed in cerebellum white matter as well as granular cell layer (GCL) of cerebellum following all exposures. These results indicate that in utero exposure to nicotine and chlorpyrifos, alone and in combination produced significant sensorimotor deficits in male and female offspring, differential increase in brain AChE activity, a decrease in the surviving neurons and an increased expression of GFAP in cerebellum in adult offspring rats at a corresponding human adult age. Collectively, this study demonstrates that maternal exposure to environmental neurotoxic chemicals, i.e., nicotine and chlorpyrifos leads to developmental abnormalities in the offspring that persist latter into adulthood.

Administration, Topical↗
PubMed2000

Time window of intracisternal osteogenic protein-1 in enhancing functional recovery after stroke.

Osteogenic protein-1 (OP-1, BMP-7) is a member of the bone morphogenetic protein subfamily of the TGF-ss superfamily that selectively stimulates dendritic neuronal outgrowth. In previous studies, we found that the intracisternal injection of OP-1, starting at one day after stroke, enhanced sensorimotor recovery of the contralateral limbs following unilateral cerebral infarction in rats. In the current study, we further explored the time window during which intracisternal OP-1 enhances sensorimotor recovery, as assessed by limb placing tests. We found that intracisternal OP-1 (10 microg) given 1 and 3 days, or 3 and 5 days, but not 7 and 9 days after stroke, significantly enhanced recovery of forelimb and hindlimb placing. There was no difference in infarct volume between vehicle- and OP-1-treated animals. The mechanism of OP-1 action might be stimulation of new dendritic sprouting in the remaining uninjured brain.

Animals↗
PubMed2001

A comparison of 129S2/SvHsd and C57BL/6JOlaHsd mice on a test battery assessing sensorimotor, affective and cognitive behaviours: implications for the study of genetically modified mice.

Mice from the 129S2/SvHsd (129) and C57BL/6JOlaHsd (C57) strains were assessed for performance on a test battery including sensorimotor, affective and cognitive measures, using established as well as modified paradigms. Marked strain differences were observed in measures of locomotion, motor coordination and anxiety: the 129 mice were typically less active and more anxious. In contrast, the strains did not markedly differ in muscular strength, habituation to an open field or spatial working memory. The data provide baseline parameters of behaviour against which genetically modified lines derived from these particular parental strains can be assessed.

Affect↗
PubMed2002

SR 141716A prevents delta 9-tetrahydrocannabinol-induced spatial learning deficit in a Morris-type water maze in mice.

This study reports a series of spatial discrimination procedures in a Morris-type maze to investigate the effects of delta9-tetrahydrocannabinol (delta9-THC) on different phases of learning and memory in mice. Adult male mice were given training trails to find the submerged platform at a fixed location in the water maze adapted for mice. In additional experiments, mice were trained with the repeated acquisition procedure to test the working memory. Results indicate that delta9-THC (8 mg/kg i.p.) 30 min pretest impaired specifically the acquisition of spatial learning and the performance of mice in the working memory task, while consolidation and retrieval of a previously learned task were not affected. There was no evidence of motoric difficulty, as the number of quadrant line crossings was not decreased and no visible sign of sensorimotor disturbance was observed during swimming. Pretreatment with SR 141716A (1 mg/kg i.p.), a CB1 cannabinoid receptor antagonist, significantly prevented the learning deficits in the water maze. These findings show that delta9-THC impairs spatial discrimination learning in a selective way in the water maze in mice and that these deficits may be mediated by cannabinoid receptors.

Animals↗
PubMed1990

Autonomic correlates of stuttering and speech assessed in a range of experimental tasks.

Electrodermal activity, peripheral blood flow, and heart rate were recorded from 19 stutterers and 19 normal speakers during performance of jaw movements, a strenuous breath-holding task, reading, and spontaneous speech. The tasks were selected to produce a range of autonomic activation and thus help scale autonomic activation for speech relative to other motor behaviors. Speaking was associated with relatively large increases in autonomic activity in both stutterers and normal speakers. There were no differences between the two groups of speakers, suggesting that the stutterers did not have abnormally high levels of autonomic activation in speech. Within the group of stutterers, the more extreme increases in arousal (specifically increases in measures reflecting sympathetic arousal) were correlated with the occurrence and increased severity of disfluent speech. Significant correlations were found for the intervals prior to, during, and after speech. Although significantly correlated with disfluency, measures of autonomic arousal accounted for small percentages of the variances of fluency and severity. The results are consistent with the hypothesis that sympathetic arousal accompanies the breakdowns in speech motor processes characteristic of stuttering. Mechanisms linking autonomic nervous system functions and somatic sensorimotor processes involved in speech production are discussed.

Adolescent↗
PubMed2001

Levels of cognitive and linguistic development in Angelman syndrome: a study of 20 children.

Angelman syndrome (AS) is a genetic disorder associated with severe developmental delay. The purpose of this study was to investigate cognitive and linguistic development in AS. Piaget's developmental model was used to evaluate the test results. The participants comprised 20 children (14 boys and 6 girls) aged 2-14 years (median age 7.4 years). AS was diagnosed either according to typical clinical criteria or confirmatory genetic testing. Cognitive functioning was evaluated with Griffiths' Mental Development Scale. Language development was also evaluated with Receptive-Expressive Emergent Language Scale 2 (REEL-2). Cognitive functioning, based on results on the Performance Scale, never exceeded Piaget's sensorimotor stage, 0-2 years. The median mental age for language development was 9 months. Expressive verbal vocabulary consisted of less than 2 words (n = 11), 2-3 words (n = 7) and 4-5 words (n = 2). Analyses according to REEL-2 did not indicate a consistent discrepancy between impressive and expressive language.

Adolescent↗
PubMed1997

Role of the midbrain periaqueductal gray in maternal nurturance and aggression: c-fos and electrolytic lesion studies in lactating rats.

the upright, crouched, or kyphotic, nursing posture of lactating rats is dependent on suckling stimulation from pups. Because of the neuroanatomical connections of the periaqueductal gray (PAG) and its sensorimotor integration of the analogous lordosis posture displayed by sexually receptive female rats, the possible role of the PAG in kyphosis was investigated using c-fos immunocytochemistry and electrolytic lesions. Lactating rats interacting with and nursing a litter of suckling pups showed greater Fos-immunoreactive nuclei in the lateral and ventrolateral caudal PAG (cPAGl,vl) compared with dams receiving nonsuckling somatosensory, distal, or no stimulation from pups. In contrast, this pattern was not evident in the rostral PAG, where the highest Fos levels occurred in nonsuckled dams, or in five other brainstem sites with either no group differences (peripenduncular, dorsal raphe, and pontine nuclei) or negligible Fos (ventral tegmental area, spinal trigeminal nuclei). After bilateral electrolytic lesions of the cPAGl,vl during gestation or on day 7 postpartum, active maternal behaviors, such as retrieval and licking of pups, and total nursing time were essentially normal. Kyphotic nursing, however, was reduced by 85%, nursing in prone and supine postures increased substantially, and 24 hr litter weight gains were reduced, particularly early in lactation (by 26%). Furthermore, lesioned rats attacked a strange male twice as often as controls did, which is suggestive of reduced fearfulness. These results extend the known roles of the PAG in reproductive and defensive behaviors to the postural control of suckling-induced kyphotic nursing and the modulation of maternal aggression.

Aggression↗
PubMed1998

Anesthetics eliminate somatosensory-evoked discharges of neurons in the somatotopically organized sensorimotor striatum of the rat.

The somatotopic organization of the lateral striatum has been demonstrated by anatomical studies of corticostriatal projections from somatosensory and motor cortices and by single-cell recordings in awake animals. The functional organization in the rat, characterized thus far in the freely moving rat preparation, could be mapped more precisely if a stereotaxic, and possibly an anesthetized, preparation could be used. Because striatal discharges evoked by innocuous somatosensory stimulation are used in mapping, this study tested whether such discharges can be observed during anesthesia, encouraged by responsiveness during anesthesia in somatosensory cortical layers projecting to the striatum. Electrode tracks through lateral striatum of anesthetized rats (pentobarbital or ketamine) revealed spontaneously discharging neurons but no discharges evoked by somatosensory examination (passive manipulation and cutaneous stimulation of 14 body parts). Similar tracks in chronically implanted rats showed evoked firing at numerous sites during wakefulness but not during anesthesia (pentobarbital or urethane). Comparisons of the activity of individual neurons between wakefulness and anesthesia showed that pentobarbital, ketamine, chloral hydrate, urethane, or metofane eliminated evoked firing and suppressed spontaneous firing. Recovery time was greater for neural than for behavioral measures. Thus, mapping as proposed is ruled out, and more importantly, the data show that somatotopically organized lateral striatal neurons stop discharging in response to natural stimulation during anesthesia. Available data indicate they do not reach threshold in response to depolarizations produced by glutamatergic corticostriatal synaptic transmission projected from the somatosensory cortex. These data and demonstrations of anesthetic-induced imbalances in most striatal neurotransmitters emphasize that many results regarding striatal physiology and pharmacology during anesthesia cannot be extrapolated to behavioral conditions, thus indicating the need for more empirical testing in conscious animals.

Anesthetics↗
PubMed2003

Normal and pathological reading: converging data from lesion and imaging studies.

In this paper we discuss cognitive and anatomical models of reading that have emerged from behavioral and lesion studies of dyslexia and functional neuroimaging studies of normal subjects. We then suggest that discrepancies in their findings can partly be overcome by functional neuroimaging studies of patients with acquired dyslexia. We present two such studies. One patient had a large left temporoparietal lesion which limited his reading to words with high semantic associations. When he read these words aloud, activation was observed in all areas of the normal reading system with the exception of the damaged left superior temporal lobe. The second patient had anterior temporal lobe atrophy with semantic dementia and a deficit in reading words that rely on lexical or semantic mediation. When asked to read aloud words on which she was likely to succeed, she activated all the normal areas, with increased activation in a left sensorimotor area associated with phonological processing and decreased activation in several areas associated with semantic processing. By relating these findings to those from lesion studies and imaging studies of normals, we propose that the translation of orthography to phonology is mediated semantically by the anterior part of the left midfusiform gyrus. In contrast, when semantic processing is compromised, the translation of orthography to phonology will be more reliant on the posterior part of the left midfusiform and the left frontal areas associated with phonology. Future studies are required to examine the connectivity between these areas during normal and abnormal reading.

Brain↗
PubMed2001

Startle and sensorimotor gating in rats lacking CCK-A receptors.

Otsuka Long Evans Tokushima Fatty (OLETF) rats lack CCK-A receptors because of a genetic mutation. Previous studies have shown that CCK-A receptors seem to play a role in the regulation of prepulse inhibition (PPI) of the startle reflex, an operational measure of sensorimotor gating. This study investigated baseline and drug-disrupted PPI in OLETF rats and their non-mutant counterparts, Long Evans Tokushima Otsuka (LETO) rats. Baseline PPI did not differ significantly between the two rat genotypes but OLETF rats exhibited a higher acoustic startle response compared to LETO rats. Amphetamine (2 mg/kg), and the non-competitive NMDA antagonist, dizocilpine (0.1 mg/kg), disrupted PPI in LETO rats but not in the OLETF rats. Apomorphine (0.5 mg/kg) failed to disrupt PPI in both LETO and OLETF rats, and haloperidol (0.5 mg/kg) produced a comparable facilitation of PPI in both groups. In a separate study, OLETF rats were found to be less sensitive to the locomotor stimulating effects of amphetamine. These results suggest that CCK-A receptors play a significant role in the behavioral effects of amphetamine and dizocilpine. The PPI response of OLETF rats to amphetamine and dizocilpine is similar to normal rats pretreated with atypical antipsychotics, suggesting that CCK-A receptors may play an important role in the restoration of drug-disrupted PPI by antipsychotics.

Acoustic Stimulation↗
PubMed1990

Selective short- and long-term effects of serotonin, small cardioactive peptide, and tetanic stimulation on sensorimotor synapses of Aplysia in culture.

Synapses between the sensory and motor cells of Aplysia can be enhanced by heterosynaptic or homosynaptic stimulation. We have used the isolated sensorimotor synapse of Aplysia in cell culture to explore short- and long-term heterosynaptic facilitation produced by 2 facilitatory transmitters and compared these to homosynaptic facilitation produced by posttetanic potentiation. We found that brief application of 5-HT or small cardioactive peptide (SCP) evokes comparable short-lasting enhancement of nondepressed sensorimotor synapses. The effect evoked by SCP diverges from that of 5-HT when the sensorimotor synapse is first depressed by low-frequency homosynaptic stimulation. Whereas 5-HT facilitates sensorimotor synapses whether or not they are depressed, SCP has little or no effect on synapses that have been depressed by more than 75%. The 2 transmitters also differ in producing long-term facilitation. Whereas repeated applications of 5-HT evoke long-term facilitation of the synapses, SCP applications do not. To determine whether these failures to facilitate could be overcome by increasing levels of cAMP, we applied SCP in the presence of phosphodiesterase inhibitors, which resulted in SCP evoking both short- and long-term changes comparable to that of 5-HT. Homosynaptic facilitation by post-tetanic potentiation differed from heterosynaptic facilitation in that tetanic stimulation failed to evoke long-lasting changes in the synapse. These results support recent findings that 5-HT is a critical neuromodulator in behavioral sensitization and dishabituation and suggest that critical levels of cAMP may be required for long- and short-term facilitation of depressed synapses.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1996

Dextroamphetamine enhances "neural network-specific" physiological signals: a positron-emission tomography rCBF study.

Previous studies in animals and humans suggest that monoamines enhance behavior-evoked neural activity relative to nonspecific background activity (i.e., increase signal-to-noise ratio). We studied the effects of dextroamphetamine, an indirect monoaminergic agonist, on cognitively evoked neural activity in eight healthy subjects using positron-emission tomography and the O15 water intravenous bolus method to measure regional cerebral blood flow (rCBF). Dextroamphetamine (0.25 mg/kg) or placebo was administered in a double-blind, counterbalanced design 2 hr before the rCBF study in sessions separated by 1-2 weeks. rCBF was measured while subjects performed four different tasks: two abstract reasoning tasks--the Wisconsin Card Sorting Task (WCST), a neuropsychological test linked to a cortical network involving dorsolateral prefrontal cortex and other association cortices, and Ravens Progressive Matrices (RPM), a nonverbal intelligence test linked to posterior cortical systems--and two corresponding sensorimotor control tasks. There were no significant drug or task effects on pCO2 or on global blood flow. However, the effect of dextroamphetamine (i.e., dextroamphetamine vs placebo) on task-dependent rCBF activation (i.e., task - control task) showed double dissociations with respect to task and region in the very brain areas that most distinctly differentiate the tasks. In the superior portion of the left inferior frontal gyrus, dextroamphetamine increased rCBF during WCST but decreased it during RPM (ANOVA F (1,7) = 16.72, p < 0.0046). In right hippocampus, blood flow decreased during WCST but increased during RPM (ANOVA F(1,7) = 18.7, p < 0.0035). These findings illustrate that dextroamphetamine tends to "focus" neural activity, to highlight the neural network that is specific for a particular cognitive task. This capacity of dextroamphetamine to induce cognitively specific signal augmentation may provide a neurobiological explanation for improved cognitive efficiency with dextroamphetamine.

Adult↗
PubMed2003

Long-term effects of delayed motherhood in mice on postnatal development and behavioural traits of offspring.

BACKGROUND: Some epidemiological evidence tentatively suggests that children born to older parents may have lower intellectual development and maturity than children whose parents are younger. This study aims to analyse the long-term effects of delayed motherhood in mice on postnatal development and behavioural traits later in life. METHODS: Hybrid females, either at the age of 10 weeks or 51 weeks, were individually housed with a randomly selected 12-14 week old hybrid male. After a postweaning resting period of 1 week, dams were caged again with a new randomly selected 12-14 week old male. This sequence of events was repeated until old females reached the end of their reproductive life. RESULTS: Delayed motherhood in mice not only had negative effects on reproductive potential but also on preweaning development of offspring as evidenced by higher mortality, retarded sensorimotor integration and lower body weights as well as on behavioural traits of young adult offspring including decreased spontaneous motor activity, lower step-through latencies in the retention trial of a passive avoidance behaviour test, and no changes in escape latencies throughout five daily sessions in a Morris water maze test. CONCLUSION: Advanced maternal age at conception may influence preweaning development and learning capacity of offspring in the mouse model.

Animals↗
PubMed1995

Experimental models and behavioural tests used in the study of Parkinson's disease.

The present review brings the survey of the most frequently used behavioural tests in experimental models of Parkinson's disease (PD). Although there is no spontaneous occurrence of parkinsonism in animals, several experimental animal models of PD have been developed to achieve the same clinical features in animals. The techniques employing neurotoxins in lesioning the nigrostriatal dopaminergic (DA) system have a large selectivity and reproducibility. The most frequently used neurotoxins are 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA). MPTP-lesioned monkeys mimic best the symptomatology of PD in human patients while rats appear to be refractory to MPTP. For that reason, 6-OHDA is used to damage the substantia nigra in a rodent model. Behavioural tests of animals with nigrostriatal lesion represent valuable non-invasive methods for assessing the influence of damaged DA system on locomotor activity. The most frequently used experimental model of PD is the drug-evoked rotation in 6-OHDA unilaterally lesioned rats. This model produces well-defined and stable behavioural deficits. The rotation test is a useful parameter for evaluating imbalances of dopamine in both striata of the hemi-parkinsonian rat model. T-maze, treadmill running test or sensorimotor tests are used to evaluate spontaneous locomotor activity of lesioned animals. Skilled motor tasks measure the influence of dopamine-depleting lesions on complex motor acts. Transplantation of DA tissue into the striatum offers a new approach to the treatment of PD. Experimental models and behavioural tests are used to evaluate the extent of graft-induced recovery of MPTP- or 6-OHDA-lesioned animals. Different results obtained after the use of different tests reflect the level of graft integration into the host circuitry.

Animals↗
PubMed1998

Inhibitory effect of A10 dopaminergic neurons of the ventral tegmental area on the orienting response evoked by acoustic stimulation in the cat.

The effect of bilateral electric stimulation of A10 dopaminergic neurons of the ventral tegmental area (80-300 microA, 20-50 Hz, 0.1-0.5 ms, 2 s duration) on latency and duration of the orienting response, evoked by acoustic stimuli (4500-8000 Hz, 2 s), was studied in the cat. A10 neuron stimulation, simultaneous with the acoustic one, was performed with threshold parameters inducing minimal behavioral signs (head searching movement, sniffing, increase in alertness). By means of a videoanalysis system, a statistically significant increase, both of latency and duration of the response, was observed. The possible role of dopamine was studied administrating sulpiride (20 mg/kg i.p.), a dopaminergic antagonist prevalently acting on the mesolimbic-mesocortical system. In this condition, the disappearance of A10 neuron effect occurred. Sulpiride injection did not affect the parameters of the orienting response to acoustic stimulus alone, suggesting a direct effect on A10 dopaminergic neurons. Moreover, when saline administration was carried out, no significant modification of the effects, obtained following A10 neuron activation, was observed. The data suggest that A10 dopaminergic neurons, origin of the mesolimbic-mesocortical system, may be involved in the control of the response to sensory stimuli, likely by influencing sensorimotor integration processes. An involvement in the inhibitory regulation of the switching of attention is also discussed.

Acoustic Stimulation↗
PubMed2000

Effects of subdural haematoma on sensorimotor functioning and spatial learning in rats.

Twenty per cent of all strokes are haemorrhagic in character and are associated with severe disturbances in sensorimotor behaviour and cognition. Although spontaneous recovery of pre-stroke functioning occurs in some cases, the process is demanding, slow, and often incomplete. A first step in the preclinical testing of new putative, neuroprotective and recovery-supporting therapeutics is to validate animal models of brain injury. In a series of four experiments we evaluated the behavioural impairments and the time course of recovery of functional deficits in rats with an experimentally induced subdural haematoma. We found that unilateral subdural haematoma resulted in dysfunction in both simple reflexive (experiment 1) and skilled sensorimotor behaviour (experiment 2). Reflexive behaviour did not recover, or recovered only marginally, and neither did the deficits in skilled forepaw use. Bilateral subdural haematoma impaired the learning and memory performance of adult (experiment 3) and old rats (experiment 4) in the Morris water escape task. Considering the diversity of the deficits found in our experiments, we conclude that different models are needed to cover the broad range of deficits seen in stroke patients.

Age Factors↗
PubMed1988

Central organization of wave localization in the clawed frog, Xenopus laevis. II. Midbrain topology for wave directions.

The organization of water wave localization within the midbrain of the clawed frog Xenopus was investigated by performing behavioral tests on frogs that had partial midbrain ablations. The criterion of localization was the orientation of turns toward the origin of impinging waves. All lesion effects became apparent as localization failure within an angular sector of wave direction. The sectors were contralateral to the lesion and of various sizes, some comprising the complete hemifield. Localization outside of the sectors was not affected. Thus, wave localization is topologically organized with respect to wave direction. Two topological projections were found. Lesions of the first projection resulted in unoriented responses to the affected wave directions. After lesions of the other projection, the frog responded to waves from the affected directions by lunges without turns. It is suggested that the two types of localization failures are due to impairment of the sensory wave direction detection and of the sensorimotor transfer, respectively. The essential midbrain areas are presumably the magnocellular nucleus of the torus magnocellularis and the ventrolateral tectum, but a considerable part of the localization might be done in the medulla.

Animals↗
PubMed1995

[The role of serotonin in behavior modulation].

The central projection systems represent an expansive and important component of the brainstem reticular core which provide modulatory input into multiple target networks throughout the entire vertebrate neuraxis. Most of the afferent input into the cranial raphe originates within sensory uni- and polymodal, associative and limbic cortices suggesting that serotonin modulates preprocessed information. The serotonergic neurons discharge in a remarkably stable and tonic fashion during wakefulness. Some 5-HT neurons increase their discharge rate phasically in association with the activation of central rhythmic pattern generators involved in consummatory and grooming behaviour. In concert with enhancing motor functions, the serotonergic systems discretely deamplify sensory attentiveness and pain processing, thereby establishing an essential and protective filter mechanism against distracting and irritating noise effects of sensory afferent input level. In addition, serotonin restrains the latency to responding, i.e. impulsivity. These effects of serotonin are mediated by multiple receptor subtypes with distinct pre- and postsynaptic localisation and regional distribution pattern, acting via amplifying (5-HT2 receptors) or desamplifying (5-HT1 receptors) G-protein-dependent transduction mechanisms. The breakdown of these protective and adaptive functions of 5-HT in complex behaviour and in basic aspects of sensorimotor integration may have a pathogenetic role in disorders of impulse control (e.g. bulimia nervosa and OCD) which have been found to respond to high-dose, long-term treatment with selective serotonin reuptake inhibitors.

Animals↗