Article

5-HT2A and alpha1b-adrenergic receptors entirely mediate dopamine release, locomotor response and behavioural sensitization to opiates and psychostimulants.

Inserm U.114, Collège de France, 11, Place Marcelin Berthelot, 75231 Paris Cedex 05, France.
European Journal of Neuroscience (Impact Factor: 3.75). 01/2005; 20(11):3073-84. DOI: 10.1111/j.1460-9568.2004.03805.x
Source: PubMed

ABSTRACT Addictive properties of drugs of misuse are generally considered to be mediated by an increased release of dopamine (DA) in the ventral striatum. However, recent experiments indicated an implication of alpha1b-adrenergic receptors in behavioural responses to psychostimulants and opiates. We show now that DA release induced in the ventral striatum by morphine (20 mg/kg) is completely blocked by prazosin (1 mg/kg), an alpha1-adrenergic antagonist. However, morphine-induced increases in DA release in the ventral striatum were found to be similar in mice deleted for the alpha1b-adrenergic receptor (alpha1b-AR KO) and in wild-type (WT) mice, suggesting the presence of a compensatory mechanism. This acute morphine-evoked DA release was completely blocked in alpha1b-AR KO mice by SR46349B (1 mg/kg), a 5-HT2A antagonist. SR46349B also completely blocked, in alpha1b-AR KO mice, the locomotor response and the development of behavioural sensitization to morphine (20 mg/kg) and D-amphetamine (2 mg/kg). Accordingly, the concomitant blockade of 5-HT2A and alpha1b-adrenergic receptors in WT mice entirely blocked acute locomotor responses but also the development of behavioural sensitization to morphine, D-amphetamine or cocaine (10 mg/kg). We observed, nevertheless, that inhibitory effects of each antagonist on locomotor responses to morphine or D-amphetamine were more than additive (160%) in naïve WT mice but not in those sensitized to either drug. Because of these latter data and the possible compensation by 5-HT2A receptors for the genetic deletion of alpha1b-adrenergic receptors, we postulate the existence of a functional link between these receptors, which vanishes during the development of behavioural sensitization.

0 Bookmarks
 · 
52 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Accumulating evidence suggests that the neuropeptide substance P (SP) and its principal receptor neurokinin 1 (NK1) play a specific role in the behavioral response to opioids and stress that may help to initiate and maintain addictive behavior. In animal models, the NK1 receptor is required for opioids to produce their rewarding and motivational effects. SP neurotransmission is also implicated in the behavioral response to stress and in the process of drug sensitization, potentially contributing to vulnerability to addiction or relapse. However, SP neurotransmission only plays a minor role in opioid-mediated antinociception and the development of opioid tolerance. Moreover, the effects of SP on addiction-related behavior are selective for opioids and evidence supporting a role in the response to cocaine or psychostimulants is less compelling. This review will summarize the effects of SP neurotransmission on opioid-dependent behaviors and correlate them with potential contributing neural pathways. Specifically, SP neurotransmission within components of the basal forebrain particularly the nucleus accumbens and ventral pallidum as well as actions within the ascending serotonin system will be emphasized. In addition, cellular- or network-level interactions between opioids and SP signaling that may underlie the specificity of their relationship will be reviewed.
    Brain research 11/2009; 1314:175-82. · 2.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lead poisoning is a potential factor in brain damage, neurochemical dysfunction and severe behavioral problems. Considering this effect, our study was carried out to investigate the effects of wormwood to restore enzymes activities, lipid peroxidation and behavioral changes induced by lead. Thirty Wistar rats were divided into five groups (n = 6 in each group): three groups exposed to 750 ppm of lead acetate in the drinking water for 11 weeks and two groups as control. Aqueous wormwood extract (200 mg/kg body weight) was administrated to intoxicated (Pb(-)+A.AB) and control groups (A.AB) for four supplemental weeks. Activities of acetylcholinesterase (AchE), monoamine oxidase (MAO) and thiobarbituric acid-reactive substances (TBARS) level were determined in the hypothalamus, hippocampus, cortex and striatum of male rats and the grooming and locomotors activity were defined in all groups. The intoxicated group (Pb) has a significantly increased TBARS value compared with the control in all regions (P < 0.05) and, after treatment with the wormwood extract, a significant reduction was noted. The enzyme activity decreased significantly (P < 0.05) in the Pb group compared with the control, essentially for the hippocampus (AchE: -57%, MAO: -41%) and the striatum (AchE: -43%, MAO: -51%). After wormwood extract administration, the AchE and MAO activity were significantly increased in all brain regions compared with the Pb group (P < 0.05). The behavioral test (locomotors and grooming test) indicates a significant hyperactivity in the Pb group compared with the control group. After treatment with wormwood extract, the Pb(-)+A.Ab indicates a lower activity compared with Pb. These data suggest that wormwood extract may play a very useful role in reduction of the neurotoxicological damage induced by lead.
    Journal of Emergencies Trauma and Shock 01/2011; 4(1):82-8.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The activity of locus coeruleus (LC) neurons has been extensively investigated in a variety of behavioural states. In fact this norepinephrine (NE)-containing nucleus modulates many physiological and pathological conditions including the sleep-waking cycle, movement disorders, mood alterations, convulsive seizures, and the effects of drugs such as psychostimulants and opioids. This review focuses on the modulation exerted by central NE pathways on the behavioural and neurotoxic effects produced by the psychostimulant methamphetamine, essentially the modulation of the activity of mesencephalic dopamine (DA) neurons. In fact, although NE in itself mediates some behavioural effects induced by methamphetamine, NE modulation of DA release is pivotal for methamphetamine-induced behavioural states and neurotoxicity. These interactions are discussed on the basis of the state of the art of the functional neuroanatomy of central NE- and DA systems. Emphasis is given to those brain sites possessing a remarkable overlapping of both neurotransmitters.
    Current Neuropharmacology 01/2013; 11(1):80-94. · 2.03 Impact Factor