Effects of MDMA, MDA and MDEA on blood pressure, heart rate, locomotor activity and body temperature in the rat involve α‐adrenoceptors

Abstract

1 The effects of injection of 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and N-ethyl-3,4-methylenedioxyamphetamine (MDEA) (all 20 mg kg À1) on blood pressure, heart rate, core body temperature and locomotor activity in conscious rats were investigated using radiotelemetry. 2 MDMA and MDA produced a prolonged increase in both systolic and diastolic pressures, with MDA causing the most marked rise. MDEA produced a transient but nonsignificant fall in diastolic pressure. The pressor response produced by MDA was accompanied by bradycardia. 3 All three amphetamine derivatives caused an initial hypothermic response; however, MDA also produced a subsequent hyperthermia, and the speed of recovery from hypothermia was MDA4 MDMA4MDEA. The a 2A -adrenoceptor antagonist 2-((4,5-dihydro-1H-imidazol-2-yl)methyl)-2,3-dihydro-1-methyl-1H-isoindole (BRL 44408) (1 mg kg À1) prolonged the hypothermic response to MDMA. 4 Only MDA induced locomotor activity when given alone, but in the presence of BRL 44408, MDMA produced increased locomotor activity. 5 The order of potency for producing isometric contractions of rat aorta (a 1D ) and vas deferens (a 1A ) was MDA4MDMA4MDEA, with MDEA acting as an a 1 -adrenoceptor antagonist with a pK B of 4.7970.12 (n ¼ 4) in aorta. 6 The order of potency for prejunctional inhibition of stimulation-evoked contractions in rat vas deferens (a 2A -adrenoceptor mediated) was MDA4MDMA4MDEA. 7 Blood pressure actions of the three amphetamine derivatives may be at least partly due to a 1 -adrenoceptor agonism or antagonism. The reversal of the hypothermic actions are at least partly due to a 2A -adrenoceptor agonism since the hypothermic response was more prolonged with MDEA which exhibits low a 2A -adrenoceptor potency, and effects of MDMA after a 2A -adrenoceptor antagonism were similar to those of MDEA.

3,4-Methylenedioxymethamphetamine- and 8-Hydroxy-2-di-n-propylamino-tetralin-Induced Hypothermia: Role and Location of 5-Hydroxytryptamine 1A Receptors

“…In most of the studies to date reporting MDMA-induced hypothermia at room temperature radiotelemetry was used to measure body temperature (Berkey et al, 1990;Bexis and Docherty, 2006). As handling and rectal temperature measurements significantly increase body temperature and serotonin release (Berkey et al, 1990;Adell et al, 1997), animals given MDMA in studies in which these methods of temperature measurement were used may have increased amounts of serotonin release over animals in which biotelemetry was used to measure temperature.…”

“…At a temperature of 30°C, however, all doses of MDMA tested increased heart rate and blood pressure (Irvine et al, 2001). Bexis and Docherty (2006) recently reported that a dose of MDMA (20 mg/kg s.c.) that caused a purely hypothermic response did not significantly affect heart rate but did increase mean arterial pressure. In our study, i.p.…”

“…Although hyperthermia remains the best studied physiologic effect related to MDMA usage, hypothermia can also occur, a phenomenon that is often ignored or, when acknowledged, is attributed to low ambient temperatures (Malberg and Seiden, 1998). MDMA, however, can evoke decreases in body temperature at normal or even elevated ambient temperatures (Malberg et al, 1996;Bexis and Docherty, 2006). Even in studies in which MDMA causes hyperthermia, a transient initial period of hypothermia or a delay in the development of hyperthermia is often seen (Gordon et al, 1991;Malberg et al, 1996).…”

“…Whereas the effects of MDMA on cutaneous blood flow have been well studied (Pedersen and Blessing, 2001), its effects on other components of the cardiovascular system are less well known. Although it causes tachycardia in humans (Lester et al, 2000), the cardiovascular effects of MDMA in rats have not been clearly delineated, as both an increase (Gordon et al, 1991) and no effect on heart rate have been reported (Irvine et al, 2001;Bexis and Docherty, 2006).…”

Aspectos neuroimunológicos do ecstasy (N-metil-3,4-Metilenodioximetanfetamina-MDMA), na inflamação alérgica pulmonar em camundongos Balb/C.

“…De fato, embora tenha sido descrito, uma ação ansiogênica do MDMA em diferentes modelos animais de ansiedade (HO et al, 2004;LIN et al, 1999;MCGREGOR, 2000;SUMNALL et al, 2004;WINSLOW;INSEL, 1990) existem evidências substâncias suportando efeitos ansiolíticos para esta droga (GURTMAN et al, 2002; GURTMAN et al, 2002). Neste sentido, outros estudos mostraram que ratos pré-tratados com MDMA, tendem a apresentar uma diminuição da freqüência de levantar, da locomoção total e da exploração em um campo aberto (GURTMAN et al, 2002;MORLEY et al, 2001;; o MDMA, também alterou a função cardiovascular (BADON et al, 2002;SEAMAN, 2003;BEXIS;DOCHERTY, 2006;JAENE;OOTSUKA;NALIVAIKO;BLESSING, 2004) e as respostas neuroquímicas ao estresse (BAUMANN et al, 2008;DE PAULA et al, 2009;MATUSZEWICH et al, 2002).…”