Volume 88, January 2008

Antagonism of phencyclidine-induced stimulus control in the rat by other psychoactive drugs



Abstract:

• It has been observed that agents with agonist activity at 5-HT2A receptors prevent neurotoxicity induced by the non-competitive NMDA antagonist, dizocilpine (MK-801).
• Subsequent behavioral studies reported complete antagonism by LSD and DOM of the stimulus effects of the related NMDA antagonist, phencyclidine [PCP].
• The present study sought to extend those observations to include other psychoactive drugs. Male F-344 rats were trained in a 2-lever, fixed-ratio 10, food-reinforced task with PCP (3.0 mg/kg; IP; 30 min pretreatment) as a discriminative stimulus.
• Tests of generalization were then conducted using the training dose of PCP in combination with a range of doses of DOM, LSD, d-amphetamine, MDMA, psilocybin, buspirone, and GHB.
• All of the drugs tested in combination with PCP produced a statistically significant diminution of PCP-appropriate responding but for none was antagonism complete.
• These data, obtained using a stimulus control model of the hallucinogenic effects of PCP, fail to support the hypothesis that LSD and DOM completely antagonize stimulus control by PCP.
• Instead, the data suggest complex interactions between PCP-induced stimulus control and a variety of psychoactive drugs including GHB, an agent with no known affinity for serotonergic receptors.

Keywords: Lysergic acid diethylamide (LSD); Phencyclidine (PCP); (−)-2,5-dimethoxy-4- methylamphetamine (DOM); d-amphetamine; Methylenedioxymethamphetamine (MDMA); Psilocybin; Buspirone; Gamma-hydroxybutyrate (GHB); Drug discrimination; Rat

LIST OF PHARMA JOURNALS

List of the Indian Journals
----------------------------
1. CIMS
2. Current Literature on Science of Science.
3. CSIR News.
4. Computers Today.
5. Chemical Weekly.
6. Drug cases.
7. DESIDOC Bulletin on Inf. Technology.
8. Dataquest Magazine.
9. EFY with Annual.
10. Industrial Product Finder.
11. IDMA bulletin.
12. Indian Drugs.
13. Indian Drug Review.
14. Indian Journal of Chemistry.
15. Indian Journal of Exp. Biology.
16. Indian journal of Chemical Technology.
17. Indian Journal of Biochem. & Biophysics.
18. Indian journal of Pharmacology.
19. Indian journal of Pharm. Education.
20. Journal of Scientific & Industrial Research.
21. Journal of Medicinal & Aromatic Plant & research.
22. Journal of Food Science and Technology.
23. MIMS.
24. Medicinal & Aromatic Plants Abstracts.
25. Medinews.26. Nandini Chemical Journal.
27. Proceedings (Chemical Sciences)
28. PTI Science Service.
29. Pharmaceutical Product Finder.
30. Express Pharma Pulse.
31. Drugs & Pharmaceutics (Industry Highlights).
32. Drugs & Pharmaceutics (Current R & D Highlights).
33. Yojana
34. Vision
35. Vikalp
36. University News
37. Udhymita Samacher Patra
38. Survey
39. Current Science
40. Data Quest
41. Management Review
42. Indian Management
43. Fortune India
44. Electronics For You
45. India Today
46. British Medical Journal
47. Business India
48. Business Today
49. Business World

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LIST II

1. Indian journal of pharmacology
2. The Indian Pharmacist
3. Journal of pharmaceutical research
4. Indian Drugs
5. IDMA Bulletin
6. Indian Journal of heterocyclic chemistry
7. Journal of Science and Pharmacy
8. Phytopharma
9. The Antiseptic
10.The Pharma review
11. Indian journal of biotechnology
12. Medicinal and aromatic plants: abstracts
13. Indian journal of Experimental biology
14. Indian journal of chemistry : Section A
15. Indian journal of chemistry: Section B
16. Indian journal of pharmaceutical sciences
17. Agro India
18. Biomed
19. Annual review of pharmacology and toxicology
20. WHO Bulletin
21. WHO Drug Information
22. Pharmaceuticals and biologicals


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GENE EXPRESSION

• Gene expression, or simply expression, is the process by which a gene's DNA sequence is converted into the structures and functions of a cell.
• Non-protein coding genes (e.g. rRNA genes, tRNA genes) are not translated into protein.
• Gene expression is a multi-step process that begins with transcription of DNA, which genes are made of, into messenger RNA.
• It is then followed by post transcriptional modification and translation into a gene product, followed by folding, post-translational modification and targeting.
• The amount of protein that a cell expresses depends on the tissue, the developmental stage of the organism and the metabolic or physiologic state of the cell. ---------------------------------------------------------------------------------------------
  
• Patterns of gene expressionNumerous terms are used to describe patterns of gene expression, including: A constitutive gene → is a gene that is transcribed continually compared to a facultative gene which is only transcribed when needed. A housekeeping gene → is typically a constitutive gene that is transcribed at a relatively constant level. The housekeeping gene's products are typically needed for maintenance of the cell. It is generally assumed that their expression is unaffected by experimental conditions. Examples include actin, GAPDH and ubiquitin. A facultative gene → is a gene which is only transcribed when needed compared to a constitutive gene. An inducible gene → is a gene whose expression is either responsive to environmental change or dependent on the position of the cell cycle.
  
• Measurement

1. Indirectly, the expression of particular genes may be assessed with DNA microarray technology, which can provide a rough measure of the cellular concentration of different messenger RNAs; often thousands at a time. While the name of this type of assessment is actually a misnomer, it is often referred to as expression profiling.
2. The expression of many genes is known to be regulated after transcription, so an increase in mRNA concentration need not always increase expression.
3. A more sensitive and more accurate method of relative gene expression measurement is real-time polymerase chain reaction. With carefully constructed standard curve it can even produce an absolute measurement such as in number of copies of mRNA per nanolitre of homogenized tissue, or in number of copies of mRNA per total poly-adenosine RNA.
4. Protein expression levels can be measured by fusing the desired protein to another reporter protein, such as the green fluorescent protein or the enzyme beta-galactosidase. The expression level of these reporter proteins can be directly quantified using standard techniques.
   

• Regulation of gene expression

Regulation of gene expression is the cellular control of the amount and timing of appearance of the functional product of a gene. Any step of gene expression may be modulated, from the DNA-RNA transcription step to post-translational modification of a protein. Gene regulation gives the cell control over structure and function, and is the basis for cellular differentiation, morphogenesis and the versatility and adaptability of any organism.

• Overexpression

The protein encoded by a gene can be expressed in increased quantity. This can come about by increasing the number of copies of the gene or increasing the binding strength of the promoter region. Often, the DNA sequence for a protein of interest will be cloned or subcloned into a plasmid containing the lac promoter, which is then transformed into the bacterium Escherichia coli. Addition of IPTG (a lactose analog) causes the bacteria to express the protein of interest. However, this strategy does not always yield functional protein, in which case, other organisms or tissue cultures may be more effective. As for example the yeast, Saccharomyces cerevisiae, is often preferred to bacteria for proteins that undergo extensive Posttranslational modification. Nonetheless, bacterial expression has the advantage of easily producing large amounts of protein, which is required for X-ray crystallography or nuclear magnetic resonance experiments for structure determination.

• Gene networks and expression

Genes have sometimes been regarded as nodes in a network, with inputs being proteins such as transcription factors, and outputs being the level of gene expression. The node itself performs a function, and the operation of these functions have been interpreted as performing a kind of information processing within cell and determine cellular behaviour.

• Techniques Primer:

Used to facilitate expression
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