Influence Of Baclofen Research Articles

The Histologic Effect of Baclofen in Rat’s brain: An Experimental Study

Background: Baclofen is the only clinically available metabotropic GABAB receptor agonist. Several reports has been discussed the efficacy of baclofen but the available data on its effect of the behavior and brains' histology are still limited.Objectives: This work aims to assess the effects of long term exposure to baclofen (8weeks) on behavior and brains' histology in ratsMethods: Analysis of data of Twenty five healthy male Albino rats were performed. Rats weighing about 200–210 g with mean age of 65 days were randomly selected and categorized into three groups: Group 1(LD50 group): included five rats that gavaged with single dose of baclofen to test the LD50 of drug (145mg per Kg) .Group 2. (control group):included eight rats were gavaged with distilled water for 2 months. Group 3.(baclofen group): included 12 rats gavaged with 15mg/kg of baclofen (1/10th LD50) for 2 month. Behavioral Tests were conducted on all animals in group 2 and 3 including: Open-field test ,Open -field habituation task ,and object recognition(Novel) to examine the influence of drug on the cognition of rats. All animals were euthanized with ether after 24hours of last day of treatment. Brains were excised and collected from rats of group 2 and 3.Fixation of tissues was done using buffered solution of ten percent of formalin for twenty four hours with paraffin wax embedding. Sectioning and staining by hematoxylin and eosin protocol (H&E) and prepared to be examine histologically. To differentiate between the data of group 2 and 3 ,statistical analysis was performed by 1- way analysis of variance (ANOVA) .Least significant difference test with Duncan test was used . Value of P of equal or less than 0.05 means the difference is significant .Results: This study revealed that the rats of baclofen group traveled a greater total distance(in both sessions) when compared with those of control indicating their hyperactivity. The zone specific analysis showed that the rats that were administered with baclofen consumed markedly greater time nearby the walls in the peripheral part in the arena throughout the first and 2nd 15- min session in comparison with those of control group indicating the generalized hyperactivity and exploration. Rats of control group preferred the novel object in comparison with those of baclofen group. However there is no marked difference in the index of discrimination among rats of group 2 and 3. Histological sections of rats’ brains in group that were administered with 15mg/kg of baclofen for 2 month( baclofen group) revealed a diminished thickness in the pyramidal cells’ layer, irregular faintly stained cells with shrinkage in the some pyramidal nerve cells, dark staining cytoplasm and losing the characteristics of their nuclei.Conclusions:Chronic administration with baclofen (15mg/kg/day/2months) induces changes in the brain histology in rats, however, baclofen has no adverse effect on the behavior. To the best of our information, our work is the 1st that focus on the influence of baclofen on both the behavior and brains' histology. Our data suggesting that baclofen may have clinical utility.

Influence of baclofen on laryngeal and spinal motor drive during cough in the anesthetized cat

The antitussive properties of (±) baclofen on laryngeal muscle activities have not been determined. The hypothesis of this study was that administration of (±) baclofen would suppress upper airway muscle motor activity in a dose-dependent manner during cough. This is a prospective, preclinical, hypothesis-driven, paired design. Electromyograms of the parasternal, rectus abdominis, thyroarytenoid, posterior cricoarytenoid, and thyrohyoid were measured, along with esophageal pressure. Cough was elicited by mechanical stimulation of the lumen of the intrathoracic trachea in spontaneously breathing cats. Baclofen (±) (3-10 μg kg(-1) i.a.) induced decreases in the electromyogram amplitude of the rectus abdominis motor drive during coughing, the inspiratory and active expiratory (E1) phases of cough, and cough number per epoch. There was no effect of (±) baclofen on the EMG amplitudes of any of the laryngeal muscles, the parasternal, or the duration of the passive expiratory (E2) phase. Results from the present study indicate differential control mechanisms for laryngeal and inspiratory motor drive during cough, providing evidence of a control system regulating laryngeal activity and inspiratory spinal drive that is divergent from the control of expiratory spinal motoneurons.

Influence of baclofen on upper airway and spinal motor drive during cough in the anesthetized cat

The antitussive effects of (±) baclofen on upper airway muscle activities have not been determined. The hypothesis of this study was that administration of (±) baclofen would suppress upper airway muscle motor activity in a dose dependent manner during cough. Electromyograms (EMGs) of the parasternal, rectus abdominis, thyroarytenoid, posterior cricoarytenoid, and thyrohyoid muscles were measured along with esophageal pressure. Cough was elicited by mechanical stimulation of the lumen of the intrathoracic trachea. Baclofen (±) (3 – 10 μg kg−1 i.a.) induced decreases in EMG amplitude of the rectus abdominis during coughing and cough number per epoch. The durations of the inspiratory and expiratory (E1) phases of cough were prolonged by (±) baclofen. There was no effect of (±) baclofen on the EMG amplitudes of any of the laryngeal muscles, the parasternal, or the duration of the expiratory (E2) phase. Results from the present study indicate differential control mechanisms for laryngeal and spinal muscle motor drive during cough, providing evidence of a control system regulating upper airway activity that is divergent from that controlling drive to spinal motoneurons during cough. Supported by NIH HL89104, HL103415.

Baclofen influences acquisition and MMP-2, MMP-9 levels in the hippocampus of rats after hypoxia

BackgroundBaclofen, the agonist of GABAB receptors, influences hypoxia-induced deficits in learning and memory processes. MethodsWe studied the effects of baclofen on acquisition in the passive avoidance test and in the Morris water maze in groups of rats without or after hypoxia as well as the influence of baclofen on MMP-2 and MMP-9 levels in the hippocampus. ResultsEven though baclofen itself impaired the acquisition in the passive avoidance, it improved the hypoxia-induced deficit of acquisition in the passive avoidance test and in the Morris water maze. There was a significant decrease in the level of the active form of MMP-2 as well as an increase in the level of pro-MMP-9 in the hippocampus of rats without hypoxia 30min after the administration of baclofen. Furthermore, an elevated level of pro-MMP-9 was observed 30min after hypoxia. Baclofen used before the deprivation of oxygen, decreased the level of the active form of MMP-2 and pro-MMP-9. ConclusionsThese results show that MMP-2 and MMP-9 activities in the hippocampus can be regulated by baclofen in non-pathological conditions and very shortly after hypoxia induction. We suggest that the changes in MMP-2 and MMP-9 levels are the mechanism activities of baclofen in the acquisition process.

Influence of baclofen and group I mGluR ligands on activity of rats in the Porsolt test

Influence of baclofen and group I mGluR ligands on activity of rats in the Porsolt test

Influence of baclofen on temperature sensitive neurons in chick hypothalamus

The effects of the GABA(B)-receptor agonist baclofen on neuronal tonic activity (firing rate) and temperature sensitivity (temperature coefficient, TC) of neurons in the preoptic area/anterior hypothalamus (PO/AH) have been examined in chick brain slices, using extracellular recordings. The tonic activity of both warm-sensitive and cold-sensitive neurons, as well as temperature-insensitive neurons, was significantly inhibited by superfusion with baclofen (1 microM). It is clearly evident from the present study that there was an increasing trend in warm-sensitive neurons and a significant (p<0.05) increase in TC of cold-sensitive neurons. Relatively high percentage (31.5%) of chick PO/AH neurons was determined as cold sensitive by present investigation. Particularly, GABA(B) mechanisms modify temperature sensitivity of the PO/AH neurons and thus modulation of temperature sensitivity in PO/AH is involved in the control of body temperature.

The GABAB agonist baclofen blocks the expression of sensitisation to the locomotor stimulant effect of amphetamine.

The purpose of the present study was to test the possible influence of baclofen, a GABAB agonist, on the long-term sensitisation to amphetamine in rats. As expected, chronic amphetamine treatment (1.5 mg/kg i.p. daily for 10 days) led to an increased locomotor response to amphetamine (0.75 mg/kg i.p.), when the animals were challenged 20 days after the end of repeated treatment. Baclofen (2 mg/kg i.p.), administered before the test session, did not significantly modify the spontaneous locomotor activity of rats, but decreased the normal and, to a greater extent, the sensitised locomotor response to amphetamine; thus baclofen prevented the expression of sensitisation to amphetamine. Moreover a previous chronic treatment with baclofen (2 mg/kg i.p. daily for 10 days) attenuated the amphetamine-induced locomotor activity in sensitised, but not in control animals. This effect was observed 20 days after the last baclofen administration. In conclusion, the present results demonstrate that GABAB receptors play an important role in the expression of the sensitised behavioural response to amphetamine and further support a potential role of GABAB agonists in the treatment of psychostimulant addiction.

Baclofen and AII 3–7 on Learning and Memory Processes in Rats Chronically Treated With Ethanol

KUZIEMKA-ŁȨSKA, M., H. CAR, AND K. WIŚNIEWSKI. The effect of baclofen and AII 3–7 on learning and memory processes in rats chronically treated with ethanol. PHARMACOL BIOCHEM BEHAV 62(1) 39–43, 1999.—The aim of this study was to determine the possible influence of baclofen, an agonist of the GABAB receptor on behavioral activity (recall, acquisition of conditioned reflexes) of angiotensin II fragment 3–7 (AII 3–7) in rats chronically treated with ethanol. Long-term (9 weeks) ethanol intoxication profoundly impaired learning and memory processes in all tests used. The GABAB receptor agonist baclofen (0.75 mg/kg IP) did not influence exploratory and motor activity in the control rats, but we observed a tendency (without significance) to decrease the psychomotor activity in the alcohol-intoxicated groups of animals, when it was injected together with AII 3–7 (2 μg ICV). Baclofen did not influence the retrieval process in the passive avoidance recall, and when it was given together with AII 3–7 did not change the positive action of this fragment in control groups, but significantly enhanced its action in the animals chronically treated with ethanol. Baclofen showed significant improvement of acquisition in the active avoidance test only in the alcohol-intoxicated groups. Baclofen, injected together with AII 3–7, yielded important attenuation action of AII 3–7 in the control groups in the first 3 days of test, but did not produce any changes during the fourth and fifth day of the experiment. Baclofen did not provoke any changes in activity of AII 3–7 (when it was injected together) in the acquisition of the active avoidance test in the alcohol-intoxicated groups of animals.

Phaclofen-sensitive GABA-B receptors do not mediate excitatory effects of baclofen on gastric secretion.

The present study investigates the effects of centrally or peripherally administered baclofen on gastric acid secretion from pylorus-ligated rats. The influence of baclofen on basal acid secretion from isolated guinea-pig gastric fundus was also evaluated. At all doses employed, intracerebroventricular baclofen significantly decreased acid secretion, this inhibitory action being antagonized by intracerebroventricular phaclofen. Intravenous baclofen induced both gastric inhibitory and excitatory responses at low and high doses, respectively. Intracerebroventricular phaclofen prevented the inhibitory effect, while neither intracerebroventricular nor intravenous phaclofen modified the stimulant action of parenteral baclofen. Both central and parenteral muscimol did not influence gastric acid secretion. Moreover, baclofen or muscimol were without effect on basal acid secretion from isolated guinea-pig gastric fundus, whereas bethanechol caused a marked and concentration-dependent stimulant action. The present results provide further evidence for the inhibitory role of central phaclofen-sensitive GABA-B receptors in the regulation of acid secretion. In addition they indicate that the hypersecretory effect exerted by parenteral baclofen may depend upon the activation of putative peripheral non-A and phaclofen-insensitive GABA-B receptors. Finally, peripheral GABA receptors do not appear to be significantly involved in the direct control of gastric secretion.