2003, Number 6
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Salud Mental 2003; 26 (6)
Avances en la investigación básica de los efectos in vivo de los disolventes de abuso
Páez-Martínez N, López-Rubalcava C, Cruz SL
Language: Spanish
References: 61
Page: 8-16
PDF size: 315.52 Kb.
ABSTRACT
This paper reviews the in vivo effects of organic solvents under conditions relevant to solvent abuse, i.e., when exposure to high concentrations for brief periods of time occurs. Whenever available, comparisons between the efficacy and potency of different compounds are presented. To give a general overview of the compounds involved in this review, a table comparing the physico-chemical properties of some of the most important solvents is included. Most of the behavioral effects of solvents have been assessed using static and dynamic exposure chambers to deliver them via inhalation, but the use of the i.p. route is not rare. Dynamic chambers are preferred for chronic studies, because the continuous flow of solvents and air prevents CO
2 accumulation. Studies using these techniques have provided evidence that several abused solvents share stimulus-discriminative effects with Central Nervous System (CNS) depressants such as benzodiazepines, barbiturates, and ethanol. Conversely, they do not substitute for morphine (an opioid agonist) or chlorpromazine (a dopamine antagonist). The reinforcing properties of solvents have also been tested in animals. Rhesus monkeys administer themselves thinner, diethyl ether or toluene, while mice and rats show conditioned place preference associated to toluene administration. These effects are consistent with reports indicating that toluene increases dopamine release in the mesolimbic system. Toluene and TCE, like other CNS depressants, produce a biphasic effect on locomotor activity; i.e., an increase at relatively low concentrations and an increase at higher concentrations. For this effect, toluene is at least eight times more potent than TCE. Based on the similarity in the behavioral effects of solvents and CNS depressants, solvents have been tested for anticonvulsant properties. Toluene and xylene acutely protect against pentylenetetrazol-induced convulsions while toluene does the same against NMDA-induced seizures. These findings provide further support, in vivo, to the in vitro NMDA-receptor antagonism and positive GABAA-receptor modulation previously described for solvents. The anxiolytic-like effects of toluene were initially described in the Geller-Seifter procedure and the plus-maze test. Recently, these findings have been extended to other compounds using different experimental paradigms. In a comparative study, several commonly abused solvents showed anxiolytic-like effects in the conditioned defensive burying behavior paradigm. The order of potency to produce these effects was toluene › benzene › 1,1,1-trichloroethane (TCE) › diethyl-ether, with toluene being at least 10 times more potent than diethyl ether. Flurothyl, a proconvulsant solvent with high lipophilicity and volatility, had no effect on this test. In an other study, the effects of toluene and TCE were tested on nociception. Toluene produced an increase in mechano-nociception while TCE lacked an effect. In contrast, both solvents increased thermonociception in the hot plate test, with toluene being four times more potent than TCE. In a comparative study of the effects of several solvents pertaining to the group of hydrocarbons in the hot plate test, cyclohexane and ethylbenzene increased thermonociception, while hexane, benzene, and propylbenzene did not. These findings reveal that the effects on nociception cannot be generalized even for closely chemicallyrelated compounds. The cellular mechanisms involved in these effects have not been described and are the subject of ongoing investigation. There are relatively few reports concerning the effects of chronic exposure to solvents. Tolerance to the acutelyinduced ataxia has been described. Also, there is evidence that sensitization occurs to the increase in locomotor activity produced by toluene. A mild state of physical dependence to TCE and toluene has been observed in animals chronically exposed to them, evidenced by handling-induced convulsions. Prenatal exposure to solvents has been associated with low weight at birth, perinatal death and cranial/facial abnormalities. All together, these findings provide a more comprehensive knowledge of the in vivo effects of commonly abused solvents and point out the need to conduct more chronic studies to understand the neuronal basis of abstinence, tolerance and sensitization to their effects
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