Progress in neuro-psychopharmacology & biological psychiatry
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Prog. Neuropsychopharmacol. Biol. Psychiatry · May 2004
Effect of inescapable tones on behavioral despair in Wistar rats.
The present experiment investigated the potentially differential effects of presenting inescapable tones with progressively increasing or decreasing durations on performance in behavioral despair, an animal model of depression based on two forced swim tests. Groups of female Wistar rats (n=8 each) were exposed to 60 inescapable tones (2000 Hz, 120 dB) either in a series of increasing or decreasing durations. Duration of tone exposure was incrementally increased (from 1 to 10 s) or decreased (from 10 to 1 s) by 1 s every six trials. ⋯ Animals were exposed to a 15 min forced swim test a day after tone (or control) treatment, followed by a 5 min swim test 24 h later. Analyses were done on diving, jumping, head shakes, duration and time of onset of immobility for the two swim tests. Compared to controls, animals that received tone exposure displayed greater immobility in the second swim test, indicating aggravation of behavioral despair due to inescapable tones.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Jan 2004
Clozapine and cocaine effects on dopamine and serotonin release in nucleus accumbens during psychostimulant behavior and withdrawal.
There is an increasing awareness that a psychosis, similar to that of schizophrenic psychosis, can be derived from cocaine addiction. Thus, the prototypical atypical antipsychotic medication, clozapine, a 5-HT(2)/DA(2) antagonist, was studied for its effects on cocaine-induced dopamine (DA) and serotonin (5-HT) release in nucleus accumbens (NAcc) of behaving male Sprague-Dawley laboratory rats with In Vivo Microvoltammetry, while animals' locomotor (forward ambulations), an A(10) behavior, was monitored at the same time with infrared photobeams. Release mechanisms for monoamines were determined by using a depolarization blocker, gamma-butyrolactone (gammaBL). ⋯ Subacute studies (a) suggest that withdrawal responses occurred in the cocaine group, based on recorded deficiencies in monoamine neurotransmitters (b) show that withdrawal effects in the cocaine group likely presynaptic, were distinguished from locomotor behavior, classically known to be mediated postsynaptically, and finally, (c) suggest that clozapine, with longer lived pharmacokinetic properties, reversed 5-HT cocaine-related withdrawal effects, but was unable to reverse DA cocaine-related withdrawal responses. Taken together with data from this laboratory, in which the 5-HT(2A/2C) antagonist, ketanserin, affected cocaine neurochemistry in much the same way as did clozapine, a mediation by either separate or combined 5-HT(2A/2C) receptors for these clozapine/cocaine interactions, is suggested. Further studies, designed to tease out the responses of selective 5-HT(2A) and 5-HT(2C) receptor compounds to cocaine and clozapine/cocaine, are underway.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Jan 2004
Anticonvulsant and antiepileptogenic effects of GABAA receptor ligands in pentylenetetrazole-kindled mice.
Although animal models based on pentylenetetrazole (PTZ) are widely used, the mechanism by which PTZ elicits its action is not very well understood. At the molecular level, a generally accepted mechanism of PTZ is noncompetitive antagonism of the gamma-aminobutyric acid (GABA)(A) receptor complex. By a systematic pharmacological investigation of various GABA(A) receptor ligands, our aim was to gain a better understanding of the GABAergic mechanisms involved in different PTZ-induced seizures. ⋯ The agonist 4,5,6,7-tetrahydroisoxazolo-(5,4-c)pyridin-3-ol (THIP) was devoid of both anticonvulsant and antiepileptogenic effects. Marked differences in drug sensitivity were observed between models based on single and chronic administration of PTZ showing that the two sets of models are fundamentally different. These results describe the pharmacology of a set of ligands believed to bind to different sites at the GABA(A) receptor complex in animal models based on PTZ and demonstrate that a drug's action in these models cannot be readily explained by agonistic or antagonistic properties at the receptor level.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Sep 2003
Multicenter StudyEfficacy and safety of levodopa with entacapone in Parkinson's disease patients suboptimally controlled with levodopa alone, in daily clinical practice: an international, multicentre, open-label study.
The combination of entacapone with levodopa is effective in the treatment of Parkinson's disease (PD), providing significant improvements in 'on' time and Unified Parkinson's Disease Rating Scale (UPDRS) motor and ADL scores in controlled clinical trials. This multicentre, open-label study was designed to further evaluate the effectiveness of levodopa combined with entacapone 200 mg in routine clinical practice. Patients experiencing end-of-dose wearing-off were treated for 8 weeks (treatment phase), with an optional extension phase up to 20 weeks. ⋯ Mean change in the total PDQ-39 scores showed improvements from baseline of -4.0 score points to the end of the treatment phase (n=182) and -3.1 score points at the end of the extension phase (n=152). Entacapone in combination with levodopa was generally well tolerated: 40 patients (8.4%) discontinued treatment due to adverse events (AEs) by the end of the extension phase. This study in a daily clinical practice setting confirmed the efficacy of coadministering entacapone with levodopa shown in controlled clinical trials and suggests that the combination is useful in improving the disability and QoL in patients with PD.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Sep 2003
Acute and subacute effects of risperidone and cocaine on accumbens dopamine and serotonin release using in vivo microvoltammetry on line with open-field behavior.
In vivo microvoltammetry was used to detect dopamine (DA) and serotonin (5-HT) release from nucleus accumbens (NAcc) of freely moving, male, Sprague-Dawley laboratory rats, while animals' locomotor (forward ambulations) and stereotypic behavior (fine movements of sniffing and grooming) were monitored at the same time with infrared photobeams. Monoamine release mechanisms were determined by using a depolarization blocker (gamma-butyrolactone, gamma BL). Miniature carbon sensors (BRODERICK PROBES microelectrodes) smaller than a human hair were used in conjunction with a semidifferential electrochemical circuit to detect release of each monoamine in separate signals and within seconds. ⋯ Thus, (a) these studies were able to tease out pharmacologically the critical differences between presynaptic and postsynaptic responses to drug treatment(s) and these differences may lead to more effective therapies for schizophrenic and/or cocaine psychosis. (b) Taken together with other data, these acute studies suggest that risperidone may possibly act via inhibition of presynaptic autoreceptors to produce the observed increases in accumbens DA and 5-HT release, whereas cocaine may be acting at least in part via serotoninergic modulation of DA postsynaptically. The subacute data suggest that pharmacokinetics may play a role in risperidone's action and that neuroadaptation may play a role in the mechanism of action of cocaine. Finally, the ability of risperidone to block cocaine-induced psychostimulant neurochemistry and behavior during acute studies while diminishing the withdrawal symptoms of cocaine during subacute studies suggests that risperidone may be a viable pharmacotherapy for cocaine psychosis and withdrawal.