Psicoestimulantes menores consumidos por estudiantes de la Universidad San Francisco Xavier de Chuquisaca, 2019 / Minor psychostimulants consumed by students of San Francisco Xavier de Chuquisaca University, 2019

El objetivo del estudio fue determinar el consumo de psicoestimulantes en estudiante de la Universidad San Francisco Xavier de Chuquisaca. Se recolectaron los datos mediante encuestas aplicadas a 331 estudiantes. El estudio reveló el psicoestimulante de mayor consumo con 31,88% el café y la coca cola con 26,65%, en su mayoría fueron consumidos con fines académicos. En los efectos secundarios, la sed se estableció como el más frecuente en estudiantes con 30,74%, seguido por cefalea con 27,56% y el cansancio en 14,84%. Se concluye que el café se determina como psicoestimulante menor más consumido en épocas de actividad académica y la sed como el efecto secundario más frecuente.

The objective of the study was to determine the consumption of psychostimulants in a student at the San Francisco Xavier de Chuquisaca University. The data were collected through surveys applied to 331 students. The study revealed the psychostimulant with the highest consumption with 31.88%, coffee and coca cola with 26.65%, most of which were consumed for academic purposes. Regarding side effects, thirst was established as the most frequent in students with 30.74%, followed by headache with 27.56% and fatigue in 14.84%. It is concluded that coffee is determined as the minor psychostimulant most consumed in times of academic activity and thirst as the most frequent side effect.

Neuroanatomical relationship between type 1 cannabinoid receptors and dopaminergic systems in the rat basal ganglia.

Dopamine and endocannabinoids are neurotransmitters known to play a role in the activity of the basal ganglia motor circuit. While a number of studies have demonstrated functional interactions between type 1 cannabinoid (CB1) receptors and dopaminergic systems, we still lack detailed neuroanatomical evidence to explain their relationship. Single- and double-labeling methods (in situ hybridization and immunohistochemistry) were employed to determine both the expression and localization of CB1 receptors and tyrosine hydroxylase (TH) in the basal ganglia. In the striatum, we found an intense signal for CB1 receptor transcripts but low signal for CB1 receptor protein, whereas in the globus pallidus and substantia nigra we found the opposite; no hybridization signal but intense immunoreactivity. Consequently, CB1 receptors are synthesized in the striatum and mostly transported to its target areas. No co-expression or co-localization of CB1 receptors and TH was found. In the caudate-putamen, globus pallidus and substantia nigra, TH-immunoreactive fibers were interwoven with the CB1 receptor-immunoreactive neuropil and fibers. Our data suggest that the majority of the striatal CB1 receptors are located presynaptically on inhibitory GABAergic terminals, in a position to modulate neurotransmitter release and influence the activity of substantia nigra dopaminergic neurons. In turn, afferent dopaminergic fibers from the substantia nigra innervate CB1 receptor-expressing striatal neurons that are known to also express dopamine receptors. In conclusion, these data provide a neuroanatomical basis to explain functional interactions between endocannabinoid and dopaminergic systems in the basal ganglia.

The role of the D(2) dopamine receptor (D(2)R) in A(2A) adenosine receptor (A(2A)R)-mediated behavioral and cellular responses as revealed by A(2A) and D(2) receptor knockout mice.

The A(2A)R is largely coexpressed with D(2)Rs and enkephalin mRNA in the striatum where it modulates dopaminergic activity. Activation of the A(2A)R antagonizes D(2)R-mediated behavioral and neurochemical effects in the basal ganglia through a mechanism that may involve direct A(2A)R-D(2)R interaction. However, whether the D(2)R is required for the A(2A)R to exert its neural function is an open question. In this study, we examined the role of D(2)Rs in A(2A)R-induced behavioral and cellular responses, by using genetic knockout (KO) models (mice deficient in A(2A)Rs or D(2)Rs or both). Behavioral analysis shows that the A(2A)R agonist 2-4-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine reduced spontaneous as well as amphetamine-induced locomotion in both D(2) KO and wild-type mice. Conversely, the nonselective adenosine antagonist caffeine and the A(2A)R antagonist 8-(3-chlorostyryl)caffeine produced motor stimulation in mice lacking the D(2)R, although the stimulation was significantly attenuated. At the cellular level, A(2A)R inactivation counteracted the increase in enkephalin expression in striatopallidal neurons caused by D(2)R deficiency. Consistent with the D(2) KO phenotype, A(2A)R inactivation partially reversed both acute D(2)R antagonist (haloperidol)-induced catalepsy and chronic haloperidol-induced enkephalin mRNA expression. Together, these results demonstrate that A(2A)Rs elicit behavioral and cellular responses despite either the genetic deficiency or pharmacological blockade of D(2)Rs. Thus, A(2A)R-mediated neural functions are partially independent of D(2)Rs. Moreover, endogenous adenosine acting at striatal A(2A)Rs may be most accurately viewed as a facilitative modulator of striatal neuronal activity rather than simply as an inhibitory modulator of D(2)R neurotransmission.

Interaction between the serotoninergic and dopaminergic systems in d-fenfluramine-induced activation of c-fos and jun B genes in rat striatal neurons.

To test for the relative contributions of the dopaminergic and serotoninergic systems in the striatum to the effects of d-fenfluramine, an indirect serotonin receptor agonist, we assessed the expression of Fos/Jun proteins induced by d-fenfluramine given alone or in the presence of dopaminergic or serotoninergic agents. To determine the neuronal targets of d-fenfluramine in the striatum, we identified the phenotypes of striatal neurons in which d-fenfluramine induced Fos expression. Our results demonstrated that d-fenfluramine evokes nuclear expression of Fos/Jun B proteins in the striatum, and that the Fos expression was dose-dependent and accompanied by transient induction of c-fos mRNA. Fos expression was blocked by p-chloroamphetamine, a serotoninergic neurotoxin. Pretreatment with SCH 23390, a D1-dopamine receptor antagonist, led to a marked decrease in Fos/Jun B expression in the caudoputamen, but not in the cortex, whereas pretreatment with methiothepin, a nonselective serotonin 5-HT1 receptor antagonist, blocked Fos expression completely in the cortex and only partially in the caudoputamen. The expression of Fos/Jun B in the striatum occurred mainly in dynorphin-containing neurons and in a subpopulation of striatal interneurons that exhibited NADPH-diaphorase activity. Most of the enkephalin-containing neurons of the striatum did not show Fos/Jun B staining. These results suggest that the mechanism by which d-fenfluramine induces c-fos and jun B expression in the rat caudoputamen depends at least in part on activation of the dopaminergic system by serotonin.

Up-regulation of neuronal NO synthase immunoreactivity in opiate dependence and withdrawal.

RATIONALE: Nitric oxide (NO) has been postulated to contribute significantly to analgesic effects of opiates as well as to the development of tolerance and physical dependence to morphine. OBJECTIVE: The present study was undertaken to determine the effect of chronic morphine treatment and abstinence on the expression of neuronal NO synthase (neuronal NOS, nNOS) in several brain regions of mice. METHODS: Seven days after the implantation of a 75 mg morphine pellet, adult male CD1 mice received a SC dose of 1 mg/kg naloxone. Fifteen minutes after the naloxone injection, brains were removed and nNOS expression was studied by using immunohistochemical methods. RESULTS: Morphine-dependence produced an increase in the number of nNOS-positive cells in the main and accessory olfactory bulb, olfactory nuclei, cerebellum, locus coeruleus, medulla oblongata (nucleus of the solitary tract and prepositus hypoglossal nucleus), and a decrease in nNOS immunoreactivity in hypothalamus. The administration of naloxone to morphine-dependent mice to induce abstinence increased nNOS immunoreactivity in the hypothalamus and locus coeruleus. CONCLUSIONS: These results indicate that the chronic treatment with morphine leads to alterations in nNOS expression in important regions implicated in the physical tolerance and dependence to opiates and suggest the use of specific inhibitors of this isoform in these conditions.

Inhibition of morphine withdrawal by lamotrigine: involvement of nitric oxide.

We studied the effects of lamotrigine [3,5-diamino-6-(2,3-dichlorophenyl)- 1,2,4-triazine], a new antiepileptic compound, on naloxone-precipitated morphine withdrawal in mice. Pretreatment with lamotrigine (5-100 mg/kg, s.c.) reversed in a dose-dependent way the withdrawal-induced increase in cerebellar Ca(2+)-dependent nitric oxide (NO) synthase activity and reduced the number of escape jumps and other motor symptoms of abstinence, at doses that did not modify locomotor activity (25-50 mg/kg). Pretreatment with the NMDA receptor antagonist MK-801 [(+)-5-methyl-10,11-dihydroxy-5H- dibenzo[a,d]cyclohepten-5,10-imine; dizocilpine] (0.1-0.3 mg/kg, s.c.) also reversed the increase in cerebellar Ca(2+)-dependent NO synthase activity. However, although MK-801 reduced the number of escape jumps and other motor symptoms of abstinence, its effects were not clearly dose-dependent. Furthermore, the highest dose of MK-801 tested (0.3 mg/kg) caused an impairment of the locomotor behaviour in naive mice. Thus, lamotrigine may represent a new and useful agent for the treatment of opiate abstinence.

Effects of trepelennamine on brain monoamine turnover in morphine dependent and abstinent mice.

Previous studies have reported that the histamine H1 receptor blocker tripelennamine potentiates morphine withdrawal. In this paper, the in vivo effects produced by tripelennamine on the turnover of serotonin (5-HT), dopamine (DA) and noradrenaline (NA) in the whole brain, excluding the cerebellum, were studied in control, morphine-dependent (by SC implantation of a 75 mg morphine pellet) and morphine-dependent male CD1 mice just before naloxone-precipitated withdrawal. Tripelennamine (1-10 mg/kg) was administered SC 45 min. before the animals were killed. Serotonin, 5-hydroxyindole-3-acetic acid (5-HIAA), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and noradrenaline were measured by high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) was measured by HPLC coupled with fluorimetric detection. Ratios 5-HIAA/ 5-HT, DOPAC + HVA/DA and MHPG/NA were taken as an index of serotonin, dopamine and noradrenaline turnovers, respectively. Tripelennamine (1 and 10 mg/kg) significantly reduced serotonin turnover in control and morphine-dependent mice, and potentiated the serotonin turnover reduction when it was administered 30 min before naloxone injection. The dopamine turnover was diminished by tripelennamine (1 and 10 mg/kg) in the morphine-dependent group. Tripelennamine (10 mg/kg) reduced noradrenaline turnover during abstinence. These results suggest that the potentiation of opiate abstinence by tripelennamine could be related to its antiserotonergic profile.

Correlation between brain nitric oxide synthase activity and opiate withdrawal.

The opiate withdrawal induced by administration of naloxone to morphine-dependent mice correlates with an increment of calcium- dependent nitric oxide synthase (NOS) activity in the cerebellum. L-NAME, an irreversible competitive inhibitor of NOS (0.5, 5, 25, 50 mg/kg) injected sc. 45 min. prior to naloxone significantly reduced the number of escape jumps and other motor symptoms of abstinence. In addition, L-NAME also decreased NOS activity in cerebellum. L-arginine, but not D-arginine, when coadministered with L-NAME, prevented both the inhibition of NOS activity and the reduction of withdrawal symptoms induced by L-NAME in morphine-withdrawn animals. These results demonstrate a hyperactivity of the L-arginine: NO pathway in opiate withdrawal and suggests the possibility of a therapeutic use of NOS inhibitors in this state.

Changes induced by sodium cromoglycate in brain catecholamine turnover in morphine dependent and abstinent mice.

The effects of sodium cromoglycate (CRO) were studied in relation to the metabolism of brain catecholamines: dopamine (DA) and noradrenaline (NA), and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG). CRO was injected SC in control mice, morphine-tolerant mice (tolerance was induced by SC implantation of a 75 mg morphine pellet; CRO was administered on day 4 of addiction) and 30 min before abstinence (withdrawal was induced by SC injection of naloxone (1 mg/kg) on day 4 of addiction). Brain catecholamines and their metabolites were measured using high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD), for DA, NA, DOPAC and HVA, and coupled with fluorescence detection for MHPG. The ratios of DOPAC + HVA/DA and MHPG/NA were kept as an index of DA and NA turnovers, respectively. CRO administered 30 min before naloxone-precipitated withdrawal diminished significantly NA levels in frontal cortex. CRO increased DA turnover in striatum and frontal cortex in naive animals and significantly diminished DA levels in frontal cortex and DOPAC levels in frontal cortex and midbrain in morphine-dependent mice. These findings are discussed in relation to the protective effects of CRO on opiate withdrawal and the effects of CRO on locomotor activity.