Effects of (-)-ephedrine on locomotion, feeding, and nucleus accumbens dopamine in rats

Abstract

The intent of the present study was to determine the effects of systemic injections of the sympathomimetic agent ephedrine (EPH) on extracellular dopamine (DA) levels within the rat nucleus accumbens (NAC) and to compare these effects with those of EPH on locomotion and on feeding. In experiment 1, adult male rats were prepared with an indwelling 3 mm microdialysis probe positioned within the NAC. The rats were injected (i.p.) with vehicle, 5, 10, or 20 mg/kg (-)-EPH with dialysates collected every 20 min for 100 min after drug injection. Systemic injections of 5, 10 or 20 mg/kg (-)-EPH significantly enhanced extracellular levels of NAC DA over baseline by 79%, 130%, and 400%. Systemic injection of 20 mg/kg EPH significantly reduced NAC levels of DOPAC and HVA by 37% and 31%. The effects of EPH on brain dopamine activity were stereospecific given that an additional group of rats injected with 20 mg/kg (+)-EPH exhibited smaller changes in NAC DA (< 25%), DOPAC (< 10%), and HVA levels (< 20%) than did rats injected with 20 mg/kg (-)-EPH. In experiment 2, adult male rats were injected (i.p.) with 0, 5, 10, or 20 mg/kg (-)-EPH prior to placement in automated activity chambers. Total distance traveled was significantly increased by 10 and 20 mg/kg (-)-EPH, but not by 5 mg/kg (-)-EPH. In experiment 3, adult male rats were injected (i.p.) with 0, 2.5, 5, or 10 mg/kg (-)-EPH or with 0, 2.5, 5, or 10 mg/kg (+)-EPH prior to a 30-min feeding test. Although each EPH enantiomer decreased feeding, (-)-EPH was more potent in feeding suppression than was (+)-EPH. The present results suggest that EPH may alter locomotion and feeding via an indirect action on brain dopamine activity.

Interrupting activator protein‐1 signaling in conscious rats can modify neuropeptide Y gene expression and feeding behavior of phenylpropanolamine

“…1999) treatment. These drugs are AMPH‐like anorectic drugs and are classified as sympathomimetic agents that may exert their effect via the activation of monoaminergic system in the brain (Wellman et al. 1998; Cheng and Kuo 2003; Alexander et al.…”

“…Except the current finding in PPA treatment, several evidence reveal that c-fos and/or c-jun genes are activated following AMPH , methAMPH (Shilling et al 2006), ephedrine (Blandini et al 1997) or pseudoephedrine (Kumarnsit et al 1999) treatment. These drugs are AMPH-like anorectic drugs and are classified as sympathomimetic agents that may exert their effect via the activation of monoaminergic system in the brain (Wellman et al 1998;Cheng and Kuo 2003;Alexander et al 2005;Nelson and Gehlert 2006). Except sympathomimetic agents, it has been suggested that psychostimulant and opiate drugs, such as AMPH and cocaine, may target at similar immediate early gene (c-fos and c-jun) to induce behavioral responses (Torres and Horowitz 1999).…”

Noradrenergic modulation of ephedrine‐induced hypophagia

“…The sympathomimetic agent ephedrine (EPH) has wide use and misuse in the United States, including in cough and cold preparations (Tinsley and Watkins, 1998), stimulant formulations (Gruber and Pope, 1988;Kanayama et al, 2001, Martin et al, 1971, as well as preparations which purport to reduce eating, stimulate thermogenesis, and reduce body weight (Astrup et al, 1995;Malchow-Moller et al, 1981). EPH is a racemic mixture of (Ϫ)-EPH and (ϩ)-EPH enantiomers, of which the (Ϫ)-EPH enantiomer exerts a stronger behavioral action than does the (ϩ)-EPH enantiomer (Arch et al, 1982;Fairchild and Alles, 1967;Walker et al, 1993;Wellman et al, 1998). The behavioral actions of EPH have been strongly linked to the effects of EPH on dopamine (DA) neurotransmission (Angrist et al, 1977;Zarrindast, 1981;Zarrindast et al, 1987).…”

“…The behavioral actions of EPH have been strongly linked to the effects of EPH on dopamine (DA) neurotransmission (Angrist et al, 1977;Zarrindast, 1981;Zarrindast et al, 1987). For example, EPH induces the formation of the early gene product, c-fos, in DA terminal fields within the caudate nucleus (Blandini et al, 1997) and increases the extracellular concentration of DA in brain (Ruwe et al, 1985;Wellman et al, 1998). The impact of EPH on DA pathways is likely to contribute to the behavioral activating (Angrist et al, 1977;Fairchild et al, 1967;Miller et al, 1999;Walker et al, 1993) and reinforcing properties of EPH (Chait, 1994;Shannon et al, 1982;Wellman et al, 1998).…”

Anti-Hypotensive Treatment and Endothelin Blockade Synergistically Antagonize Exercise Fatigue in Rats under Simulated High Altitude

“…In rats, ephedrine doses of 20 mg/kg i.p. (12.1% of the intraperitoneal LD 50 of ephedrine in rats) increases locomotion, which provided the basis for the dosage used in this study [29], [30].…”