Effects of Methamphetamine, Dopamine and Noradrenaline Administered into the Nucleus Accumbens of Rats Discriminating Subcutaneous Methamphetamine

Ando, Kiyoshi; Miyata, Hisatsugu; Yanagita, Tomoji

doi:10.1254/jjp.64.35

Cited by 13 publications

(3 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1976; Svensson and Ahlenius 1982; Plaznik et al. 1985; Ando et al. 1994) and underlie the potent kinetic anti‐Parkinson effect of levodopa (which has higher efficacy than that of dopamine agonists, see Guttman et al.…”

Section: Discussionmentioning

confidence: 99%

Marked dissociation between high noradrenaline versus low noradrenaline transporter levels in human nucleus accumbens

Tong

Hornykiewicz

Furukawa

et al. 2007

Journal of Neurochemistry

View full text Add to dashboard Cite

We recently identified a noradrenaline-rich caudomedial subdivision of the human nucleus accumbens (NACS), implying a special function for noradrenaline in this basal forebrain area involved in motivation and reward. To establish whether the NACS, as would be expected, contains similarly high levels of other noradrenergic markers, we measured dopamine-b-hydroxylase (DBH) and noradrenaline transporter in the accumbens and, for comparison, in 23 other brain regions in autopsied human brains by immunoblotting. Although the caudomedial NACS had high DBH levels similar to those in other noradrenaline-rich areas, the noradrenaline transporter concentration was low (only 11% of that in hypothalamus). Within the accumbens, transporter concentration in the caudal portion was only slightly (by 30%) higher than that in the rostral subdivisions despite sharply increasing rostrocaudal gradients of noradrenaline (15-fold) and DBH. In contrast, the rostrocaudal gradient in the accumbens for the serotonin transporter and serotonin were similar (2-fold increase). The caudomedial NACS thus appears to represent the only instance in human brain having a striking mismatch in high levels of a monoamine neurotransmitter versus low levels of its uptake transporter. This suggests that noradrenaline signalling is much less spatially and temporally restricted in the caudomedial accumbens than in other noradrenaline-rich brain areas. The nucleus accumbens (NACS) is, in the human, a small area of the basal forebrain adjacent to the caudate nucleus, putamen and ventral septum that is considered to play an important role in rewarding and motivational function, likely mediated by the neurotransmitter dopamine (Wise 2004;Roitman et al. 2005;Epstein et al. 2006). In extension of the original observation of Farley and Hornykiewicz (1977), reporting, inter alia, high amount of noradrenaline in the human NACS, we recently reported that in the human NACS the distribution of noradrenaline is highly heterogeneous, with the caudomedial portion of the nucleus having a strikingly high concentration of the neurotransmitter; thus, this NACS subdivision represents the only area in human brain having equally high levels of both noradrenaline and dopamine (Tong et al. 2006). In view of the existing data in the human, it is somewhat surprising that the mammalian NACS is still assumed to contain little or no noradrenaline (see McKittrick and Abercrombie 2007). Although the biological significance of noradrenaline in the NACS is hypothetical, the high level of the neurotransmitter (similar to that in other noradrenaline-rich areas of human brain, see below) implies a role for noradrenaline in accumbens function in the human. In this regard, experimental animal studies have disclosed higher levels of the a 2A noradrenergic receptor in NACS than in the caudate/putamen (Talley et al. 1996). Similarly, intra-accumbens rather than caudate/putamen injection of an a 1 -noradrenergic antagonist produces behavioural inhibition (Stone et al. 2004).Received January...

show abstract

Section: Discussionmentioning

confidence: 99%

Marked dissociation between high noradrenaline versus low noradrenaline transporter levels in human nucleus accumbens

Tong

Hornykiewicz

Furukawa

et al. 2007

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…At high training doses (e.g., 1-2 mg/kg in rats) the cue is centrally mediated, whereas at low training doses the cue is peripherally mediated (Colpaert et al 1976;Stolerman and D'Mello 1981). The centrally mediated cue induced by relatively high training doses appears to be mediated by mesolimbic DA systems, since intra-accumbens (but not intra-striatal) test injections of amphetamine generalize to systemically administered amphetamine (Nielsen and Scheel-Kruger 1986;Druhan et al 1993;Ando et al 1994; see also Schechter et al 1992 for similar data with the cathinone stimulus, and Emmett-Oglesby 1989 andCallahan et al 1994 for similar data with the cocaine stimulus). The hypothesis that the amphetamine cue is mediated at mesolimbic sites is further supported by evidence that 6-OHDA lesions of the nucleus accumbens can antagonize amphetamine discrimination (Dworkin and Bimle 1989).…”

Section: Introductionmentioning

confidence: 99%

Dopamine ligands and the stimulus effects of amphetamine: animal models versus human laboratory data

Goudie

Wit

1997

Psychopharmacology

View full text Add to dashboard Cite

Studies with laboratory animals have consistently demonstrated a role for dopamine in mediating the discriminative stimulus (i.e., interoceptive) effects of amphetamine. For example, D2 dopamine agonists mimic the discriminative stimulus effects of amphetamine and D1 and D2 dopamine antagonists generally block them. The discriminative stimulus effects of drugs in animals are believed to parallel their subjective effects in humans. Therefore, it is often assumed that dopamine plays a role in amphetamine-induced subjective effects in humans and it would be reasonable to expect that dopamine antagonists would block the subjective effects of amphetamine. Few studies have tested this hypothesis directly, and those that have have yielded inconsistent results. This paper will review data regarding the effects of dopamine agonists and antagonists on the discriminative stimulus effects of amphetamine in animals and its subjective effects in humans. Possible explanations for the discrepancies between animal and human data will be discussed, and classical assumptions underlying the use of animal models of drug effects will be examined.

show abstract

“…Several investigators have shown that the route of administration can affect the outcome of the behavioral endpoint. For example, the dose required for METH or AMP stimulus control in rats was 5-fold lower when these drugs were administered IV or subcutaneous (SC) compared with intraperitoneal (IP) administration (Ando 1975;Ando et al 1994). Gentry et al, found that the locomotor effects and stereotypical behavior of METH was dependant on the route of administration (i.e., IP or SC).…”

Section: Introductionmentioning

confidence: 99%

Bioavailability of (+)-methamphetamine in the pigeon following an intramuscular dose

Hendrickson

Hardwick

McMillan

et al. 2008

Pharmacology Biochemistry and Behavior

View full text Add to dashboard Cite

Pigeons are used frequently as subjects in behavioral pharmacology research. An advantage of the pigeon is an exceedingly vascular breast muscle, which is easily accessible for injections. The purpose of these studies was to provide a profile of the pharmacokinetics of (+)-methamphetamine (METH) and (+)-amphetamine (AMP), a pharmacologically active metabolite, in pigeons (n = 6) after intramuscular (IM) and intravenous (IV) dosing (0.8 mg/kg). LC-MS/MS analysis was used to determine serum concentrations of METH and AMP. A modified crossover design was used to determine the bioavailability, time to maximum concentration, total clearance, the volume of distribution, the maximal concentration, the area under the concentration-time curve (AUC), and terminal elimination half-life for METH. The route of administration did not significantly affect these pharmacokinetic parameters. The time to maximum concentration for METH and AMP following IM administration was 0.3 h. Maximum AMP serum concentrations were achieved in 2 h, irrespective of the route of administration, and these concentrations remained essentially constant for an additional 6 h. The metabolism of METH to AMP was not affected by the route of administration, and the molar ratio AMP to METH AUC values were the same (IV=0.57; IM=0.41). These results show that METH pharmacokinetics after IM administration in the pigeon are similar to IV administration. Thus IM is a reasonable route of administration for METH behavioral assays in the pigeon if sufficient time for absorption is given following the dose, and the behavioral endpoint is not dependent on the rapid input of METH following an IV dose.

show abstract

Effects of Methamphetamine, Dopamine and Noradrenaline Administered into the Nucleus Accumbens of Rats Discriminating Subcutaneous Methamphetamine

Cited by 13 publications

References 19 publications

Marked dissociation between high noradrenaline versus low noradrenaline transporter levels in human nucleus accumbens

Marked dissociation between high noradrenaline versus low noradrenaline transporter levels in human nucleus accumbens

Dopamine ligands and the stimulus effects of amphetamine: animal models versus human laboratory data

Bioavailability of (+)-methamphetamine in the pigeon following an intramuscular dose

Contact Info

Product

Resources

About