Biomedical subjects

C Salum

Publications and source records attributed to C Salum.

5 recordsLinked to original sources

PubMed2006

Fear state induced by ethanol withdrawal may be due to the sensitization of the neural substrates of aversion in the dPAG.

The neural substrate underlying the aversive effects induced by ethanol abstinence is still unclear. One candidate for such effects is the dorsal periaqueductal gray (dPAG), a core structure of the brain aversion system. The main aim of this study is to examine the role of the dPAG as a possible locus of the aversive effects following abrupt alcohol withdrawal. To this end, rats were subjected to an oral ethanol self-administration procedure, in which animals were offered 6-8% (v/v) ethanol solution for a period of 21 days followed by an abrupt discontinuation of the treatment on the two subsequent days. Control animals received control dietary fluid for similar periods of time. The effects of ethanol withdrawal were examined in the elevated plus-maze (EPM) (Exp. I), on the prepulse inhibition of startle to loud sounds (Exp. II) and on the freezing and escape responses induced by electrical stimulation of the dPAG (Exp. III). In Experiment III, rats were implanted with an electrode aimed at the dPAG and the number and duration of ultrasonic vocalizations (USVs) were also recorded in the rats that received dPAG stimulation at freezing and escape thresholds. Data obtained showed that ethanol withdrawal elicited significant "anxiety-like" behaviors, as revealed by the decrease in the number of entries into and time spent onto the open arms of the EPM. Startle reflex and prepulse inhibition remained unchanged in withdrawn animals. In addition, discontinuation from the chronic ethanol regimen caused a reduction in the stimulation thresholds for freezing and escape and in the number and duration of USVs. Together, these effects have been interpreted in the frame of a high fear state elicited by activation of the dPAG. These findings are indicative that ethanol withdrawal sensitizes the substrates of fear at the level of this midbrain structure.

Alcohol Drinking↗

PubMed2006

Dopamine and nitric oxide interaction on the modulation of prepulse inhibition of the acoustic startle response in the Wistar rat.

RATIONALE: The nitric oxide (NO)-arginine pathway is intimately connected to the release of dopamine (DA), a neurotransmitter system that may be dysfunctional in schizophrenia. Both schizophrenic patients and rats treated with DA agonists present deficits in sensorimotor gating measured by prepulse inhibition (PPI). OBJECTIVE: Our aim was to investigate the interaction between a NO synthase inhibitor, N(G)-nitro-L-arginine (L-NOARG), and the DA agonists, amphetamine (Amph), apomorphine (Apo), bromocriptine (BRC), quinpirole (QNP) and SKF38393, on the modulation of the PPI. METHODS: Male Wistar rats received two injections of either L-NOARG (40 mg/kg, i.p.) or saline, 1 h before the test, and the DA agonists or vehicle. Testing began 5 min after treatment with Amph (2 mg/kg, i.p.), Apo (0.5 mg/kg, s.c.) or QNP (0.3 mg/kg and 1.0 mg/kg, s.c.), 120 min after BRC (1 and 40 mg/kg, i.p.) and 15 min after SKF38393 (10 mg/kg, s.c.). The PPI test consisted of 60 presentations divided into pulse (100 dB), prepulse (65, 70, 75 and/or 80 dB) and prepulse + pulse. RESULTS: L-NOARG prevented the PPI disruption caused by Amph (2 mg/kg). Apo, QNP and BRC disrupted PPI, but these effects were not significantly changed by L-NOARG. SKF38393 had no significant effect on PPI whether or not preceded by L-NOARG. CONCLUSIONS: Our findings show that L-NOARG interacted with Amph, an indirect DA agonist, but not with the direct DA agonists on PPI, suggesting that NO is involved on the dopaminergic modulation of sensorimotor gating, probably by a presynaptic mechanism.

Acoustic Stimulation↗

PubMed2005

Combined treatment of ascorbic acid or alpha-tocopherol with dopamine receptor antagonist or nitric oxide synthase inhibitor potentiates cataleptic effect in mice.

RATIONALE: Drugs like haloperidol (Hal) that decrease dopamine (DA) neurotransmission in the striatum induce catalepsy in rodents and Parkinson disease-like symptoms in humans. Nitric oxide synthase (NOS) inhibitors interfere with motor activity, disrupting rodent exploratory behavior and inducing catalepsy. Catalepsy induced by NOS inhibitors probably involves striatal DA-mediated neurotransmission. Antioxidants such as ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) have also been shown to interfere with movement modulation and the DA system. OBJECTIVE: The objective of the study is to investigate if the antioxidants vitamins C and E would influence the catalepsy produced by Hal and NOS inhibitors. METHODS: The effects of the following treatments on catalepsy were examined using the hanging-bar test on male Swiss mice (25-30 g): (1) vitamin C (30-1,000 mg/kg)xHal (1 mg/kg); (2) vitamin C (90-1,000 mg/kg)xN (G)-nitro-L: -arginine (LNOARG, 10 and 40 mg/kg); (3) vitamin C (300 mg/kg)xN (G)-nitro-L: -arginine methylester (LNAME, 20-80 mg/kg); (4) vitamin C (300 mg/kg) x 7-nitroindazole (7NI, 3-50 mg/kg); (5) vitamin C (90 mg/kg i.p.) x LNOARG [40 mg/kg twice a day during 4 days (subchronic treatment)]; (7) vitamin E (3-100 mg/kg) x Hal (1 mg/kg); and (6) vitamin E (3-100 mg/kg) x LNOARG (40 mg/kg). RESULTS: Vitamin C enhanced the catalepsy produced by NOS inhibitors and Hal. Treatment with vitamin C did not affect tolerance to LNOARG cataleptic effect induced by subchronic treatment. Vitamin E potentiated the catalepsy induced by LNOARG at all doses tested; in contrast, catalepsy induced by Hal was enhanced only by the dose of 100 mg/kg. CONCLUSIONS: Results support an involvement of dopaminergic and nitrergic systems in motor behavior control and provide compelling evidence that combined administration of the antioxidants vitamins C and E with either Hal or NOS inhibitors exacerbates extrapyramidal effects. Further studies are needed to assess possible clinical implications of these findings.

Animals↗

PubMed2003

The effect of amphetamine on Kamin blocking and overshadowing.

Schizophrenic patients show deficits on stimulus salience tasks such as latent inhibition and blocking, which measure the ability to disregard irrelevant stimuli. Amphetamine-treated animals show similar deficits in analogous tasks, thereby providing a model of the stimulus-selection deficits observed in schizophrenia. In two experiments, the effect of the indirect dopamine (DA) agonist D-amphetamine sulphate (1.0 mg/kg, i.p.) on Kamin blocking and overshadowing were examined and compared, in the rat, using the conditioned lick suppression procedure. The aim was to provide some insight into the behavioural and pharmacological mechanisms underlying amphetamine effects in both paradigms. In experiment 1, it was shown that amphetamine selectively disrupted Kamin blocking, when given either at stage 2 alone, or at both stages of the task. In experiment 2, amphetamine treatment significantly abolished Kamin blocking and overshadowing, when administered prior to compound conditioning in both tasks. These data suggest that dopamine may play a critical role in mediating performance in tasks measuring stimulus salience processes. The results are discussed in the framework of the role of DA in stimulus-selection performance.

Amphetamine↗

PubMed2000

Anxiety-like behavior in rats: a computational model.

This work describes a neural network model of the rat exploratory behavior in the elevated plus-maze, a test used to study anxiety. It involves three parameters: drive to explore; drive to avoid aversive stimuli; and spontaneous locomotor activity. Each network unit corresponds to a specific location in the maze and the connections, only between closest neighbors, represent the possible adjacent places to which a virtual rat can navigate. Competitive learning is used to generate a sequence of network states that correspond to the virtual rat successive locations in the maze. To evaluate the generality of the model it was also tested for two modifications of the elevated plus-maze: one with totally closed arms and the other with totally open arms. The results are compared with data obtained with rats. The simulations are consistent with experimental evidence and may provide an efficient way of describing the anxiety-like rat behavior in the elevated plus-maze. This could be useful for researching the emotional parameters involved in this anxiety animal model.

Animals↗