_OUTPUT_ $VAR1 = { 'section' => { ############################################################ 'subchap1' => ###[ { 'head1' => 'Introduction and History', 'para' => "Their place in textbooks of neuropsychopharmacology was a long time in coming. Although it has been known for more than 80 years that adenosine and ATP can elicit potent pharmacological effects on the cardiovascular system (Drury and Szent-Gyorgy, 1929), studies of their effects on the brain or peripheral nerves by central or systemic injection lagged approximately 20 years. The evidence that endogenous purines regulated the activity of the nervous system was not widely accepted until the 1990s when molecular cloning of the receptors for adenosine and ATP revealed that, like the other transmitters discussed in this book, there was cellular and regional selectivity in their expression sites in the brain, expanding their more general roles in energy metabolism to include additional intercellular signaling functions. Subsequent research on the purinergic systems of the central nervous system has established two main categories of signal transduction: sites where adenosine is the mediator (A receptors; Table 11\x{2013}1) and sites where ATP (and sometimes UTP) is the mediator, often in conjunction with either a monoamine or a neuropeptide. Subsequent work on the receptors for adenosine as a special kind of intercellular signal, a neuromodulator, but not a classic neurotransmitter, and for ATP as a cotransmitter more firmly established their different physiological roles and the pharmacological roles each system has been found to play in the brain as well as the autonomic nervous system." }, { 'head1' => 'Neurosteroids', 'para' => [ { 'content' => [ 'According to their discoverer, Etienne Baulieu, neurosteroids are those steroids that are synthesized in the nervous system either ', ' from cholesterol or by ', ' metabolism of blood-borne precursors but are found at levels in the nervous system that are independent of steroid synthesis by adrenals or gonads. Such steroids include at least two previously known steroid precursors, pregnenalone (PREG) and dehydroepiandrosterone (DHEA), that in the nervous system have effects alone or as sulfated esters. In the central and peripheral nervous systems, neurosteroid synthesis has been attributed to oligodendrocytes, astrocytes, and neurons. The peripheral benzodiazepine receptor found on the mitochondrial outer membrane has been suggested to allow cholesterol access to the P450 cleavage enzyme complex on the inner mitochondrial membrane, leading to PREG formation and subsequently to other neurosteroids (', ').' ], 'emphasis' => [ { 'style' => 'it', 'content' => 'de novo' }, { 'style' => 'it', 'content' => 'in situ' } ], 'hotlink' => { 'xref' => { 'xref' => 'f012003', 'xidtype' => 'figure' }, 'content' => "Fig. 12\x{2013}3" } }, { 'c' => "\x{3b4}", 'sub' => 'A', 'content' => [ 'In contrast to the endocrine actions of adrenal steroids on the brain, acting at a distance and at very low concentrations, neurosteroids are thought to act locally as either autocrine (acting on the cells that synthesizes them) or paracrine (acting on cells close to the site of synthesis) signals. In this manner, the ability to activate myelin synthesis in oligodendrocytes may provide a reparative effect in multiple sclerosis. In their sulfated ester forms, both PREG and DHEA have been reported to be potent regulators of GABA', ' and NMDA receptor functions, with PREG-S and DHEA-S inhibiting the effects of GABA; however, these effects on the GABA receptor are reduced if the complex contains a ', ' subunit.' ] }, { 'c' => [ "\x{3b1}", "\x{3b1}", "\x{3b1}", "\x{3b2}", "\x{3b1}", "\x{3b2}", "\x{3b1}", "\x{3b1}", "\x{3b1}", "\x{3b1}", "\x{3b1}", "\x{3b2}", "\x{3b1}", "\x{3b1}", "\x{3b1}", "\x{3b2}" ], 'content' => [ 'In addition, further characterization of the neurosteroids suggests that a small group of pregnenolone-, progesterone-, or tetrahydrodeoxycorticosterone-derived catabolites are the active moieties in the CNS, namely 3', ',5', '- and 3', ',5', '-androsterone, 3', ',5', '-THP pregnenolone, 3', ',5', '-THP allopregnenolone, 3', ',5', '-THDOC allotetrahydroDOC, 3', ',5', '-THDOC tetrahydroDOC, and 3', ',5', '- and 3', ',5', '-androstanol (Morrow, 2007). These are the neurosteroids that are believed to be responsible for the largely GABA-enhancing actions to induce anxiolytic, sedative, and anticonvulsant activity through allosteric modifications at discrete sites on the receptor. Of interest is that systemic doses of ethanol at low to moderate pharmacological levels induce elevation of neurosteroids to levels capable of modifying GABA receptors and contributing to the cellular and behavioral effects of ethanol (see ', ').' ], 'hotlink' => { 'xref' => { 'xref' => 'c018', 'xidtype' => 'text' }, 'content' => 'Chapter 18' } } ] } ##]##, ############################################################ 'head' => '11 Purinergic Pharmacology', 'subsecp' => { 'sub' => '1', 'char' => [ '\'', '\'' ], 'content' => [ 'P2Y receptor antagonists have been proposed as potential neuroprotective agents in the brain by modulation of Glu-induced currents at AMPA receptors and by excessive activation of glutamate receptor systems generically implicated in the apoptotic cellular death associated with stroke, epileptic seizures, and neurodegenerative diseases such as Alzheimer', 's disease, Parkinson', 's disease, and amyotrophic lateral sclerosis. Endogenous ATP has been claimed to be involved in the regulation of anxiety via stimulation of P2Y', ' receptors in the dorsomedial hypothalamus in rats. Currently, none of these therapeutic entities are known to be in the developmental pipeline.' ] }, 'cid' => 'c011', 'secnum' => '11' } }; _EXPECTED OUTPUT_ $VAR1 = { 'section' => { ############################################################ 'subsec1' => ##[## { 'h1' => 'Introduction and History', 'p' => "Their place in textbooks of neuropsychopharmacology was a long time in coming. Although it has been known for more than 80 years that adenosine and ATP can elicit potent pharmacological effects on the cardiovascular system (Drury and Szent-Gyorgy, 1929), studies of their effects on the brain or peripheral nerves by central or systemic injection lagged approximately 20 years. The evidence that endogenous purines regulated the activity of the nervous system was not widely accepted until the 1990s when molecular cloning of the receptors for adenosine and ATP revealed that, like the other transmitters discussed in this book, there was cellular and regional selectivity in their expression sites in the brain, expanding their more general roles in energy metabolism to include additional intercellular signaling functions. Subsequent research on the purinergic systems of the central nervous system has established two main categories of signal transduction: sites where adenosine is the mediator (A receptors; Table 11\x{2013}1) and sites where ATP (and sometimes UTP) is the mediator, often in conjunction with either a monoamine or a neuropeptide. Subsequent work on the receptors for adenosine as a special kind of intercellular signal, a neuromodulator, but not a classic neurotransmitter, and for ATP as a cotransmitter more firmly established their different physiological roles and the pharmacological roles each system has been found to play in the brain as well as the autonomic nervous system." }, { 'h1' => 'Neurosteroids', 'p' => [ { 'content' => [ 'According to their discoverer, Etienne Baulieu, neurosteroids are those steroids that are synthesized in the nervous system either ', ' from cholesterol or by ', ' metabolism of blood-borne precursors but are found at levels in the nervous system that are independent of steroid synthesis by adrenals or gonads. Such steroids include at least two previously known steroid precursors, pregnenalone (PREG) and dehydroepiandrosterone (DHEA), that in the nervous system have effects alone or as sulfated esters. In the central and peripheral nervous systems, neurosteroid synthesis has been attributed to oligodendrocytes, astrocytes, and neurons. The peripheral benzodiazepine receptor found on the mitochondrial outer membrane has been suggested to allow cholesterol access to the P450 cleavage enzyme complex on the inner mitochondrial membrane, leading to PREG formation and subsequently to other neurosteroids (', ').' ], 'emphasis' => [ { 'style' => 'it', 'content' => 'de novo' }, { 'style' => 'it', 'content' => 'in situ' } ], 'hotlink' => { 'xref' => { 'xref' => 'f012003', 'xidtype' => 'figure' }, 'content' => "Fig. 12\x{2013}3" } }, { 'cap' => "\x{3b4}", 'sub' => 'A', 'content' => [ 'In contrast to the endocrine actions of adrenal steroids on the brain, acting at a distance and at very low concentrations, neurosteroids are thought to act locally as either autocrine (acting on the cells that synthesizes them) or pcrine (acting on cells close to the site of synthesis) signals. In this manner, the ability to activate myelin synthesis in oligodendrocytes may provide a reptive effect in multiple sclerosis. In their sulfated ester forms, both PREG and DHEA have been reported to be potent regulators of GABA', ' and NMDA receptor functions, with PREG-S and DHEA-S inhibiting the effects of GABA; however, these effects on the GABA receptor are reduced if the complex contains a ', ' subunit.' ] }, { 'cap' => [ "\x{3b1}", "\x{3b1}", "\x{3b1}", "\x{3b2}", "\x{3b1}", "\x{3b2}", "\x{3b1}", "\x{3b1}", "\x{3b1}", "\x{3b1}", "\x{3b1}", "\x{3b2}", "\x{3b1}", "\x{3b1}", "\x{3b1}", "\x{3b2}" ], 'content' => [ 'In addition, further characterization of the neurosteroids suggests that a small group of pregnenolone-, progesterone-, or tetrahydrodeoxycorticosterone-derived catabolites are the active moieties in the cNS, namely 3', ',5', '- and 3', ',5', '-androsterone, 3', ',5', '-THP pregnenolone, 3', ',5', '-THP allopregnenolone, 3', ',5', '-THDOc allotetrahydroDOc, 3', ',5', '-THDOc tetrahydroDOc, and 3', ',5', '- and 3', ',5', '-androstanol (Morrow, 2007). These are the neurosteroids that are believed to be responsible for the largely GABA-enhancing actions to induce anxiolytic, sedative, and anticonvulsant activity through allosteric modifications at discrete sites on the receptor. Of interest is that systemic doses of ethanol at low to moderate pharmacological levels induce elevation of neurosteroids to levels capable of modifying GABA receptors and contributing to the cellular and behavioral effects of ethanol (see ', ').' ], 'hotlink' => { 'xref' => { 'xref' => 'c018', 'xidtype' => 'text' }, 'content' => 'chapter 18' } } ] } ## ]##, ############################################################ 'head' => '11 Purinergic Pharmacology', 'subsecp' => { 'sub' => '1', 'char' => [ '\'', '\'' ], 'content' => [ 'P2Y receptor antagonists have been proposed as potential neuroprotective agents in the brain by modulation of Glu-induced currents at AMPA receptors and by excessive activation of glutamate receptor systems generically implicated in the apoptotic cellular death associated with stroke, epileptic seizures, and neurodegenerative diseases such as Alzheimer', 's disease, Parkinson', 's disease, and amyotrophic lateral sclerosis. Endogenous ATP has been claimed to be involved in the regulation of anxiety via stimulation of P2Y', ' receptors in the dorsomedial hypothalamus in rats. currently, none of these therapeutic entities are known to be in the developmental pipeline.' ] }, 'cid' => 'c011', 'secnum' => '11' } };