Dietary supplementations of amino acids: evidence for enhanced serotonergic functions following haloperidol withdrawal in rat medial prefrontal cortex

To investigate the effects of orally supplemented amino acids L-Tryptophan [Trp] and L-Valine [Val] in rats repeatedly injected with haloperidol following one week of drug withdrawal, with particular reference to extrapyramidal symptoms [EPS] and serotonin [5-hydroxytryptamine; 5-HT] metabolism in medial prefrontal cortex [mPFC]. Experimental study. Place and Duration of Study: Department of Biochemistry, University of Karachi from December 2007 to February 2008. The study was conducted on thirty six locally bred male Albino Wistar rats. Freshly prepared amino acids [Val and Trp] were added in the drinking water of rats on alternate days and haloperidol at doses of 5.0 mg/kg or saline were injected twice daily for three weeks following one week of withdrawal. Locomotor/ exploratory activities were scored in activity boxes and open field apparatuses. Catalepsy was monitored on an inclined surface. The animals tested for locomotor activity and catalepsy for two weeks follow-up post-injections plus one week of drug withdrawal were decapitated to collect mPFC regions of rat brain for neurochemical analysis by high performance liquid chromatography with electrochemical detection [HPLC-EC]. There was significant increase [p < 0.01] in locomotor activity in rats orally supplemented with Val and Trp following one week of drug withdrawal from repeated administration. Marked reduction in cataleptogenic effects of the drug was also observed. Significant [p < 0.01] increases in the brain Trp and mPFC 5-HT metabolism in Val and Trp supplemented animals were also noticed. These findings help to demonstrate the effect of dietary amino acids, in particular, Trp to potentiate mPFC serotonergic modulation of neuroleptic activity

Serotonin [1A] receptor agonism in the expression of behavioral dopaminergic supersensitivity in subchronic haloperidol treated rats

The idea that serotonin [5-hydroxytryptamine; 5-HT] is contributed in schizophrenia has long been advocated and alterations in 5-HT neurotransmission has been hypothesized to modulate both the therapeutic and extrapyramidal symptoms [EPS] liability of conventional neuroleptics. The 8-hydroxy-2-[di-n-propylamino] tetralin [8-OH-DPAT], a preferential 5-HT1A ligand, has been reported to attenuate EPS functions of haloperidol in animals. In view of a possible role of 5-HT1A receptors in the management of EPS functions of a neuroleptic drug, the present study was designed to investigate behavioral responses of 8-OH-DPAT at a challenge dose of 0.5mg/kg in rats with subchronic haloperidol administration at a dose of 5mg/kg twice daily for 5 days. The intensity of 5-HT syndrome provoked by 8-OH-DPAT was taken as a measure of postsynaptic responses. In the present study administration of haloperidol at a dose of 5mg/kg twice daily for 5 days decreased locomotion significantly [p<0.01] in familiar [home cage] environment. Subchronic administration of haloperidol at the same dose elicited significant [p<0.01] cataleptic responses in rats when compared with saline treated rats. Results revealed that 8-OH-DPAT-induced hyperlocomotion [p<0.05] and forepaw treading [p<0.1] were significantly smaller in rats pre-treated with haloperidol for 5 days than repeatedly saline injected rats. Conversely, the other components of the syndrome i.e. flat body posture [p<0.001], hind limb abduction [p<0.001] and straub tail [p<0.01] were significantly greater in repeated haloperidol treated rats when compared with repeated saline injected rats. These findings help to demonstrate a causal link between the upregulation of DA-D2 receptors and the decrease in the effectiveness of presynaptic 5-HT1A receptors following subchronic haloperidol administration and this may further help to yield an antipsychotic agent with an improved profile of efficacy to EPS, thereby widening its therapeutic window

Awareness about reproductive health and rights among students of a public university in karachi, Pakistan: a cross sectional study

To determine the knowledge, attitude and practices of Karachi University students about reproductive health and rights. Cross sectional study. A survey was conducted from February to May 2005 to determine the understanding and knowledge related to reproductive health and rights among the students of the department of Biochemistry, University of Karachi, Pakistan. A pre-coded questionnaire was developed and pre-tested. The questionnaire was introduced to those students, who agreed to participate in the study. Data collected was double entered and analyzed on SPSS and Epi-info latest version. Fifty five percent [55%] of participants believed the reproductive rights to be as important as other human rights. About 80% of participants thought that proper birth spacing can improve maternal and child health but very few Pakistani women have birth spacing rights. Quality of life of women and men can be improved by knowing their reproductive rights in view of 71% and 63% of respondents respectively. Although one third of participants claimed to be aware of their reproductive rights but majority were unable to identify what exactly comes under the domain of reproductive rights. Majority knew that appropriate use of contraception and birth spacing can have positive impact on maternal and child health. The study recommends that awareness sessions should be conducted at all levels of society and more efforts should be made to improve reproductive health and increase awareness and the implementation of reproductive rights

Increase in serotonin-1A receptor responsiveness following haloperidol, withrawal

In view of a role of 5-hydroxtryptamine [serotonin; 5-HT]-1A receptors in the elicitation of extrapyramidal symptoms [EPS], The present study was designed to monitor pre- and postsynaptic responses to a selective 5 HT-1A ligand, 8-hydroxy-2- [di-n-propylamino] tetralin [8-OH-DPAT] following single and repeated [two times a day for 9 days] administration of haloperidol [5 mg/kg] in rats. The intensity of 5 H-T syndrome elicited by 8-OH-DPAT [0.5 mg/kg] was taken as measure of postsynaptic response. 8-OH-DPAT induced decreases of 5-HT metabolism in the striatum and brain were taken as a measure of postsynaptic response. 8-OH-DPAT induced forepaw treading and hyperlocomotion were smaller in haloperidol than saline injected rats. The decreases were not observed following withdrawal from repeated administration of haloperidol. Flat body posture not altered by single injection of haloperidol was enhanced following withdrawal from repeated administration of haloperidol. Haloperidol plus 8OH-DPAT injected animals exhibited comparable levels of 5-HT metabolism in the striatum as well as in the brain. Administration of 8-OH-DPAT significantly decreased 5-HT metabolism in brain but not in striatum of repeated saline injected animals. Conversely, same dose of 8-OH-DPAT injected to haloperidol-injected animals did not decrease 5-HT metabolism in the brain but decreased it in the striatum. The results show an increase in the responsiveness of pre-and postsynaptic 5-HT-responsiveness of post and presynaptic 5-HT-1A receptors may be involved in the greater incidence of EPS in patients treated with neuroleptics such as haloperidol

Serotonin and anxiety: a review of current research and clinical implications

Benzodiazepines [BNs] are known to pose risks associated with drug dependence, abuse and withdrawal symptoms. Arylpiperazines such as buspirone, gepirone and ipsapirone have been introduced as useful alternatives to/the BZs in the treatment of anxiety and depression, which are distinct illnesses and often coexist. This new class of drugs is distinguished from its predecessors by a wider margin of safety and a lower potential for fatal overdose. This article addresses salient issues and provides evidence in the burgeoning field of serotonin-related management of anxiety in clinical psychiatry

Diazepam produces regionally specific effects on brain serotonin metabolism in rats

In view of a possible role of serotonin in anxiety, the effect of low doses [1mg/kg] of diazepam on brain regional levels of tryptophan, 5 - hydroxytryp - tamine [5 -HT] and 5 - hydroxyindoleacetic acid [5 - HIAA] are investigated in rats. The concentration of tryptophan increased in the hippocampus, hypothalamus, striatum and cortex; increases in the brain stem were not significant. The concentration of 5 - HT decreased in the hippocampus, increased in the hypothalamus and cortex and cortex and remained unaltered in the striatum and brain stem. 5 - HIAA concentration decreased in the hypothalamus, increased in the striatum and remained unaltered in the hippocampus, cortex and brain stem. Possible mechanism involved in the regionally specific effects of diazepam - induced changes of brain 5 - HT metabolism and their functional significance is discussed