摘要:

Psychopathological disorders, and depression in particular, are strongly linked to eating attitude in obese patients. The identification of cannabinoid CB1 receptors (CB1Rs) in areas of the central nervous system (CNS) that have been implicated in regulation of mood and food intake suggests that these receptors may mediate such a behavioral link. The goal of this study was to evaluate CB1R modulation of antidepressant-like effects and food intake. For this purpose, 129/SVE and C57BL/6 male mice were acutely dosed intraperitoneally (i.p.) with the CB1R inverse agonist AM251 (3–30 mg/kg) and tested, respectively, in the tail-suspension test (TST) and in the forced-swim test (FST), which have been used widely as tests sensitive to antidepressant compounds. Like the antidepressant desipramine (DMI, 16 mg/kg), AM251 significantly reduced immobility at 10 mg/kg in the TST and at 1 and 10 mg/kg in the FST. Such a decrease of immobility was not accompanied by an increase in motor activity in the open field, suggesting that occupancy of CB1R by AM251 induced antidepressant-like effects. This was supported by two additional experiments. First, the co-administration of the CB1R agonist CP55940, at a dose that did not induce motor impairment or profound hypothermia (0.01 mg/kg), reversed effects of AM251 in the TST. Secondly, effects of AM251 in the FST were absent in CB1R knockout (KO) mice. In addition to an antidepressant-like effect, AM251 reduced fasting-induced hyperphagia over a comparable dose range. Taken together, these data suggest that regulation of mood and food intake might be obtained through inverse agonism of CB1R.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Cannabinoid CB1 receptor agonists, including delta-9-tetrahydrocannabinol (Δ9-THC) (the main psychoactive ingredient in marijuana) have been shown to increase feeding in rats and humans. Conversely, it has been reported that acute administration of the CB1 receptor antagonist SR 141716A reduces food intake in rats. Based upon this observation, it has been suggested that CB1 antagonists could be useful as appetite suppressant drugs. The present studies were designed to provide a detailed examination of the effects of CB1 antagonists on food intake across a range of paradigms. Two CB1 antagonists (SR 141716A and AM 251) were administered to rats trained on fixed-ratio schedules with two different ratio requirements (fixed-ratio 1 and fixed-ratio 5). Both drugs produced a dose-dependent decrease in lever pressing, and had a relatively long duration of action (T1/2: SR 141716A, 15.1 h; AM 251, 22.0 h). Furthermore, intake of three diets with differing macronutrient composition (lab chow, high fat, high carbohydrate) was studied. Both drugs significantly suppressed intake of all three foods, and there were no significant interactions between drug dose and diet type. These findings support the hypothesis that CB1 receptor antagonists could be useful pharmacological tools for the suppression of appetite.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

It is well established that the dopaminergic system influences simple reaction time (RT) performance. However, the role of this system in more complex information processing remains to be clarified. The present study was aimed at addressing this issue. To this end, we used an inferential method that relies on choice RT procedures and allows one to identify information processing stages in both humans and rats. Long–Evans rats responded to lateral visual cues (left or right). Two task factors, signal intensity and foreperiod duration, were manipulated. Low doses of two pharmacological agents, SCH 23390 (a D1receptor antagonist; 0.015 and 0.025 μmol/kg) and eticlopride (a D2receptor antagonist; 0.01 and 0.02 μmol/kg), were administrated systemically. Both drugs increased choice RT: eticlopride interacted with signal intensity on RT, showing that D2receptors mediate at least the sensory stage of stimulus preprocessing. In addition, eticlopride interacted with signal intensity on omission rate, thereby suggesting an involvement of D2receptors in attentional processes; and SCH 23390 interacted with foreperiod duration on RT, indicating that D1receptors specifically mediate the response adjustment stage. The effect of this drug on RT rests entirely in its interaction with foreperiod duration, allowing us to conclude that this D1antagonist affects the response adjustment stage while sparing all other processing stages.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

This experiment examined the effect of a 5-HT2receptor agonist DOI (2,5-dimethoxy-4-iodoamphetamine), and antagonist, ketanserin, on temporal differentiation performance. Twelve rats were trained under the free-operant psychophysical procedure to press two levers (A and B) in 50-s trials in which sucrose reinforcement (0.6 mol/l, 50 μl) was provided intermittently for responding on A during the first half, and on B during the second half of the trial. Psychometric curves were derived from percent responding on B (%B), recorded in successive 5-s epochs of the trials; logistic functions were fitted to these data for the derivation of timing indices (T50[time corresponding to %B=50%], ϵ [slope of the logistic curve], Weber fraction). Cumulative probability of switching in successive 5-s epochs was used to estimate the mean switching time,S50. DOI (0.0625, 0.125 and 0.25 mg/kg, s.c.) dose-dependently reducedT50andS50. These effects of DOI (0.25 mg/kg) were antagonized by ketanserin (1.0 mg/kg). The results show that DOI alters temporal differentiation in the free-operant psychophysical procedure. The antagonistic effect of ketanserin indicates that the effect of DOI was probably mediated by 5-HT2Arather than 5-HT2Creceptors, since ketanserin is relatively selective for 5-HT2Areceptors. Comparison of these results with our previous findings with a 5-HT1Areceptor agonist indicates that 5-HT1Aand 5-HT2Areceptors mediate qualitatively similar effects on temporal differentiation.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Pharmacological manipulations that alter dopamine (DA) at DA receptor subtypes produce reductions in feeding behaviour. What remains uncertain is the exact way in which these reductions in feeding are achieved as a consequence of differing drug actions at separate receptor subtypes. In this study our aim was to compare the anorectic effects of the preferential D3/D2agonists 7-hydroxy-2-(di-n-propylamino)tetralin (7-OH-DPAT) and quinpirole and the non-selective D2/D3antagonist raclopride on the microstructure of licking responses in non-deprived rats. In a 20-min test, trained adult, male hooded rats had access to one of three solutions: 1%, 3% or 10% sucrose. 7-OH-DPAT (0.1-1.0 mg/kg, i.p.), quinpirole (0.03–0.3 mg/kg, s.c.), raclopride (0.03–0.3 mg/kg, i.p.) or vehicle were injected 20 min prior to the start of the licking test. A lickometer recorded the timing of each lick, from which the microstructural parameters of bout frequency and bout duration were also computed. All compounds reduced the mean bout duration, while 7-OH-DPAT and raclopride also brought about a compensatory increase in bout number. Analysis of the licking rates over the test session showed that 7-OH-DPAT, quinpirole and raclopride decreased the initial rate, without affecting the rate of decline of licking. Changes in licking microstructure (i.e. initial rate of licking and mean bout duration) after the administration of 7-OH-DPAT, quinpirole and raclopride, are consistent with an action of these dopaminergic compounds to reduce palatability.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Opiate reinforcement was evaluated under a progressive ratio (PR) schedule often used for psychostimulant self-administration (termed ‘PR 3-4’ because the third response requirement was four lever presses) and three additional schedules that were modified to provide successively lower levels of difficulty by decreasing the steepness of response requirement progression (termed ‘PR 9-4’, ‘PR 14-4’, and ‘PR 26-4’ because a response requirement of four was reached with step numbers of 9, 14 and 26, respectively). With the exception of the PR 3-4 schedule, all of the schedules supported morphine self-administration, and morphine self-administration during initial exposure and reacquisition did not differ by more than 10%. In contrast to morphine, cocaine was self-administered under the PR 3-4 schedule, with responding clearly exceeding levels during extinction. The PR 9-4 schedule was most suitable for morphine self-administration because it provided an intermediate level of difficulty, which supported levels of self-administration that exceeded values obtained under extinction but were less than those observed under FR-1. Under the PR 9-4 schedule, the number of self-administered injections of morphine was 61.5% of the number of injections obtained under a simple FR-1 schedule. This compares with a value of 21.0% for cocaine self-administration under the PR 3-4 schedule compared to an FR-1 schedule. These results show important differences in self-administration behavior supported by morphine and cocaine, which are consistent with a lower reinforcing efficacy for opiates relative to psychostimulants.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The dopamine agonist apomorphine (apo) elicits stereotyped pecking bouts in pigeons, a response which increases with successive apo injections. The present study sought, first, to confirm the hypothesis that this sensitization arises through a Pavlovian conditioning driven by both external and internal cues; and, secondly, to advance the hypothesis that during this learning the dopaminergic activation only initiates a process that probably ends in glutamatergic synapse modifications. The conditioned nature of the sensitization to apo was examined in two separate experiments that compared context contingent and context uncontingent apo treatments. The role of dopaminergic mechanisms in the acquisition, maintenance and retrieval of sensitization-conditioned pecking was examined by administering the dopamine antagonist haloperidol (hal) either before, during or after apo sensitization treatments. A contingency between context and apo was found to be essential for the acquisition and retrieval of apo-sensitized pecking. A pretreatment with hal did not curtail a subsequent sensitization to apo. When hal was co-administrated with apo it suppressed the initial pecking response to apo and blocked the acquisition of sensitized responding. A pecking response normally observed when apo-sensitized pigeons are challenged with saline (sal) in the same cage in which they were sensitized, was also absent. When hal was co-administered with apo after the sensitization was complete this led at first to an only partial apo response suppression. When treated with hal in the same cage, already sensitized pigeons responded much as if they had been challenged with sal. The sensitization induced by apo was thus blocked by hal co-administered during acquisition, but during the maintenance or retrieval phase hal did not impair a previously sensitized responding. It is concluded that when pigeons are sensitized to apo, dopaminergic mechanisms are implicated in initiating the neural modifications that underlie the conditioned sensitization, but that they themselves are not importantly altered.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The purpose of the present study was to examine sensitivity to the antinociceptive effects of kappa opioids during chronic treatment with the nonselective opioid antagonist naltrexone. In a warm-water tail-withdrawal procedure, rats were restrained and the latencies to remove their tails from water maintained at 50 and 55°C were recorded. Prior to chronic treatment, spiradoline, U50,488 and (−)-pentazocine produced dose-dependent increases in tail-withdrawal latencies at both 50 and 55°C. Chronic treatment with 3.0 mg/kg naltrexone twice daily (b.i.d.) failed to alter sensitivity to the antinociceptive effects of spiradoline when tested 24 h following naltrexone administration. When the maintenance dose of naltrexone was increased to 30 mg/kg b.i.d., sensitivity to the effects of spiradoline was reduced when tested 24 h after naltrexone administration, but enhanced when tested 48 h after naltrexone administration. Enhanced sensitivity was also observed to the antinociceptive effects of U50,488 and (−)-pentazocine when tested 48 h after chronic treatment with 30 mg/kg naltrexone. After termination of chronic treatment, sensitivity to the antinociceptive effects of spiradoline, U50,488 and (−)-pentazocine returned to that originally observed prior to naltrexone treatment. These data indicate that chronic naltrexone treatment enhances sensitivity to the antinociceptive effects of kappa opioids, and that this effect is both dose and time dependent.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Using 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-D]pyrimidine (PP2), a specific inhibitor of the Src family of tyrosine kinases, here we show a direct involvement of these enzymes in memory formation and recall. When infused into the CA1 region of the dorsal hippocampus, immediately or 30 min after training rats in a one-trial inhibitory avoidance task, PP2 but not its inactive analog 4-amino-7-phenylpyrazol[3,4-D]pyrimidine (PP3), blocked short- (STM) and long-term memory (LTM) formation, as tested 2 or 24 h post-training, respectively. PP2 had no effect on STM when given at 60 min post-training or on LTM when administered at 60, 120 or 180 min after the training session, but blocked memory recall when infused into CA1 15 min before a LTM expression test. Hence, activity of the Src family of tyrosine kinases is required in the CA1 region of the rat dorsal hippocampus for the normal formation and retrieval of one-trial inhibitory avoidance memory.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID