Neurochemical effects

The various stimulants have no obvious chemical relationships and do not share primary neurochemical effects, despite their similar behavioral effects. Cocaines chemical strucmre does not resemble that of caffeine, nicotine, or amphetamine. Cocaine binds to the dopamine reuptake transporter in the central nervous system, effectively inhibiting dopamine reuptake. It has similar effects on the transporters that mediate norepinephrine and serotonin reuptake. As discussed later in this chapter in the section on neurochemical actions mediating stimulant reward, dopamine is very important in the reward system of the brain the increase of dopamine associated with use of cocaine probably accounts for the high dependence potential of the drug. 

Liu J, Olivier K, Pope CN. 1999. Comparitive neurochemical effects of repeated methyl parathion or chlorpyrifos exposures in neonatal and adult rats. Toxicol Appl Pharmacol 158 186-196. 

Salama, A.I., and Goldberg, M.E. Neurochemical effects of imipramine and amphetamine in aggressive mouse-killing (muricidal) rats. Biochem Pharmacol 19 2023-2032, 1970. 

Schmidt, C.J. Levin, J.A. and Lovenberg, W. In vitro and in vivo neurochemical effects of MDMA on striatal monoaminergic systems in rat brain. Biochem Pharmacol 36 747-755. 1987. 

The similarities in acute neurochemical effects of cocaine and amphetaminelike compounds raise the possibility that repeated exposure to cocaine might... 

Behavioural and neurochemical effects of repeated administration of cocaine in rats. Neuropharmacology 17 559-564, 1978. 

Taylor, D., and Ho, B.T. Neurochemical effects of cocaine following acute and repeated injection. J Neurosci Res 3 95-101, 1977. 

Acute and Long-Term Neurochemical Effects of Methylenedioxymethamphetamine in the Rat... 

FIGURE 10. Comparison of the neurochemical effects of the three MDA homologs 7 days after the administration of 20 mg/kg of each drug to rats... 

Schmidt, C.J. Acute administration of methylenedioxymethamphetamine Comparison with the neurochemical effects of its N-desmethyl and N-ethyl analogs. Eur J Pharmacol 136 81-88, 1987b. 

Fuller, R.W. Neurochemical effects of serotonin neurotoxins. Ann NY Acad Sci 305 178-181, 1978. 

Female NMRI mice were exposed to 100 ppm of hydrogen sulfide for 2 hours at 4-day intervals excitement was observed (Savolainen et al. 1980). Exposure also resulted in decreased cerebral ribonucleic acid (RNA), decreased orotic acid incorporation into the RNA fraction, and inhibition of cytochrome oxidase. An increase in the glial enzyme marker, 2, 3 -cyclic nucleotide-3 -phosphohydrolase, was seen. Neurochemical effects have been reported in other studies. Decreased leucine uptake and acid proteinase activity in the brain were observed in mice exposed to 100 ppm hydrogen sulfide for 2 hours (Elovaara et al. 1978). Inhibition of brain cytochrome oxidase and a decrease in orotic acid uptake were observed in mice exposed to 100 ppm hydrogen sulfide for up to 4 days (Savolainen et al. 1980). 

In vivo microdialysis has been used to evaluate the persistent neurochemical consequences of MDMA exposure in rats.88114-116 Series et al.114 carried out microdialysis in rat frontal cortex 2 weeks after a 4-day regimen of 20 mg/kg s.c. MDMA. Prior MDMA exposure did not affect baseline extracellular levels of 5-HT, but decreased levels of the 5-HT metabolite, 5-hydroxyin-doleacetic acid (5-HIAA), to 30% of control. Moreover, the ability of (+)-fenfluramine to evoke 5-HT release was markedly blunted in MDMA-pretreated rats. In an analogous investigation, Shankaran and Gudelsky115 assessed neurochemical effects of acute MDMA challenge in rats that had previously received 4 doses of 10 mg/kg i.p. MDMA. A week after MDMA pretreatment, baseline levels of dialysate 5-HT and DA in striatum were not altered even though tissue levels of 5-HT were depleted by 50%. The ability of MDMA to evoke 5-HT release was severely impaired in MDMA-pretreated rats while the concurrent DA response was normal. In this same study, effects... 

The first two antidepressants, iproniazid and imipramine, were developed in the same decade. They were shown to reverse the behavioural and neurochemical effects of reserpine in laboratory rodents, by inhibiting the inactivation of these monoamine transmitters (Leonard, 1985). Iproniazid inhibits MAO (monoamine oxidase), an enzyme located in the presynaptic neuronal terminal which breaks down NA, 5-HT and dopamine into physiologically inactive metabolites. Imipramine inhibits the reuptake of NA and 5-HT from the synaptic cleft by their transporters. Therefore, both of these drugs increase the availability of NA and 5-HT for binding to postsynaptic receptors and, therefore, result in enhanced synaptic transmission. Conversely, lithium, the oldest but still most frequently used mood stabiliser (see below), decreases synaptic NA (and possibly 5-HT) activity, by stimulating their reuptake and reducing the availability of precursor chemicals required in the biosynthesis of second messengers. 

Drug family Drug (generic) name Neurochemical effect... 

Evans, J.E., M.L. Miller, A. Andringa, and L. Hastings. 1995. Behavioral, histological, and neurochemical effects of nickel (II) on the rat olfactory system. Toxicol. Appl. Pharmacol. 130 209-220. 

Tilson, H. A., and Sparber, S. B. (1972) Studies on the concurrent behavioral and neurochemical effects of psychoactive drugs using the push-pull cannula. J. Pharmacol. Exp. Ther., 181 387-398. 

Jacobs, B. L., Wise, W. D., and Taylor, K. M. (1974) Differential, behavioral and neurochemical effects following lesions of the dorsal or median raphe nuclei in rats. Brain Res., 79 353-362. 

Hong JS, Herr DW, Hudson PM, et al. 1986. Neurochemical effects of DDT in rat brain in vivo. Arch Toxicol Suppl 9 14-26. 

Llorens J, Crofton KM, Tilson HA, et al. 1993. Characterization of disulfoton-induced behavioral and neurochemical effects following repeated exposure. Fund Appl Toxicol 20 163-169. 

Several indirect neurochemical effects of methyixanthines contribute to their effects. Micromolar concentrations of caffeine enhance release of acetylcholine (Pedata et al. 1984). However, this effect is biphasic, augmenting release at 50 pM, but decreasing it at 0.5 pM. This effect is also modulatory, affecting stimulated, but not basal, release. Caffeine enhances acetylcholine release in the hippocampus, which is due to adenosine Al receptor subtypes (Carter et al. 1995). Conversely, chronic caffeine reduces the excitatory effect of acetylcholine in the cerebral cortex (Lin and Phillis... 

The plant is used in elaborate religious ceremonies, which vary from area to area. Adherents use the plant to communicate spiritually with their ancestors. In lower doses, it is used to counteract fatigue and hunger. Warriors and hunters have used it to remain awake at night. Some Europeans have claimed that it has aphrodisiac effects as well. More recently, anecdotal reports have indicated possible antiaddictive effects of iboga, stimulating a rush of scientific research into the neurochemical effects of the plant (Mash et al. 1998). 

Copeland RL Jr, Bhattacharyya AK, Aulakh CS, Pradhan SN. (1981). Behavioral and neurochemical effects of Hydergine in rats. Arch Int Pharmacodyn Ther. 252(1) 113-23. 

Ali SF, Newport GD, Slikker W Jr, Rothman RB, Baumann MH. (1996). Neuroendocrine and neurochemical effects of acute ibogaine administration a time course evaluation. Brain Res. 737(1-2) 215-20. 

Frantz KJ, Hansson KJ, Stouffer DG, Parsons LH. 2002. 5-HT(6) receptor antagonism potentiates the behavioral and neurochemical effects of amphetamine but not cocaine. Neuropharmacology 42(2) 170-180. 

Rocha BA, Goulding EH, O Dell LE, Mead AN, Coufal NG, et al. 2002. Enhanced locomotor, reinforcing, and neurochemical effects of cocaine in serotonin 5-hydroxytrypta-mine 2C receptor mutant mice. J Neurosci 22(22) 10039-10045. 

Rats tolerated exposure to 3 00 ppm for 60 hours without clinical symptoms, although they appeared relatively inactive. At this concentration, vinyltoluene was found to accumulate in perirenal fat and was more effective than styrene, xylene, or toluene in producing neurochemical effects as determined by enzyme assays. 

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