Archival Reportα2 Adrenergic and Imidazoline Receptor Agonists Prevent Cue-Induced Cocaine Seeking
Section snippets
Animals
Male Sprague Dawley rats (initial weight 250–300 g; Charles River, Raleigh, North Carolina) were single- or pair-housed in a temperature- and humidity-controlled animal facility at the Medical University of South Carolina accredited by the Association for Assessment and Accreditation of Laboratory Animal Care. Rats were housed under a reversed 12-hour light/dark cycle (lights off at 6:00 am), with ad libitum food and water (except for food self-administration study, described below). All
Results
For all rats undergoing cocaine self-administration (n = 189), the means (± SEM) for the last 2 days of self-administration were 38.5 (±.9) and 39.6 (±1.0) infusions (approximately 20 mg/kg per day) and 54.7 (±3.7) and 53.6 (±3.2) active lever presses. The mean (± SEM) active lever presses for days 1 and 7 of extinction were 84.3 (±3.2) and 18.2 (±.8), respectively, for animals that received no treatment on extinction days. Unless noted, there were no significant differences for responding on
Discussion
Our results indicate that the I1 receptor-preferring agonist moxonidine is a potential therapeutic option for maintaining cocaine abstinence. Moxonidine reduced cocaine seeking triggered by either drug-associated cues or cocaine prime without signs of sedation. These reinstatement findings highlight the potential functional importance of the relatively unknown imidazoline signaling system in drug addiction. In addition, the current studies revealed that α2 adrenergic receptor agonists and CRF
References (72)
- et al.
Effect of environmental stressors on opiate and psychostimulant reinforcement, reinstatement and discrimination in rats: A review
Neurosci Biobehav Rev
(2003) - et al.
Alpha-2 adrenergic receptor agonists block stress-induced reinstatement of cocaine seeking
Neuropsychopharmacology
(2000) - et al.
Effects of the CRF receptor antagonist d-Phe CRF((12-41)) and the alpha2-adrenergic receptor agonist clonidine on stress-induced reinstatement of nicotine-seeking behavior in rats
Neuropharmacology
(2007) - et al.
Haloperidol antagonism of cue-elicited cocaine craving
Lancet
(1996) - et al.
Moxonidine, a selective imidazoline-1 receptor agonist, suppresses the effects of ethanol withdrawal on the acoustic startle response in rats
Biol Psychiatry
(2000) - et al.
Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats
Eur J Pharmacol
(2010) - et al.
[3H]RS79948-197 binding to human, rat, guinea pig and pig alpha2A-, alpha2B- and alpha2C-adrenoceptorsComparison with MK912, RX821002, rauwolscine and yohimbine
Eur J Pharmacol
(1998) - et al.
Effects of the CRH receptor antagonist CP-154,526 on intravenous cocaine self-administration in rats
Neuropsychopharmacology
(2000) - et al.
Repeated lofexidine treatment attenuates stress-induced, but not drug cues-induced reinstatement of a heroin-cocaine mixture (speedball) seeking in rats
Neuropsychopharmacology
(2001) - et al.
Alpha(2)-Adrenoceptor subtypes-mediated physiological, pharmacological actions
Neurochem Int
(2009)
Involvement of alpha 2-adrenoceptors in the cardiovascular effects of moxonidine
Eur J Pharmacol
Alpha2A-adrenergic receptors heterosynaptically regulate glutamatergic transmission in the bed nucleus of the stria terminalis
Neuroscience
Noradrenaline modulates transmission at a central synapse by a presynaptic mechanism
Neuron
The anxiogenic drug yohimbine reinstates methamphetamine seeking in a rat model of drug relapse
Biol Psychiatry
Selective norepinephrine reuptake inhibition by atomoxetine prevents cue-induced heroin and cocaine seeking
Biol Psychiatry
Alpha 1-noradrenergic system role in increased motivation for cocaine intake in rats with prolonged access
Eur Neuropsychopharmacol
Prazosin, an alpha-1 adrenergic antagonist, reduces cocaine-induced reinstatement of drug-seeking
Biol Psychiatry
Synergistic sedative effects of noradrenergic alpha(1)- and beta-receptor blockade on forebrain electroencephalographic and behavioral indices
Neuroscience
Combined administration of alpha1-adrenoceptor antagonist prazosin and beta-blocker propranolol impairs spatial avoidance learning on a dry arena
Behav Brain Res
Effects of CP-154,526 on responding during extinction from cocaine self-administration in rats
Eur J Pharmacol
Conditioned release of corticosterone by contextual stimuli associated with cocaine is mediated by corticotropin-releasing factor
Brain Res
Footshock stress potentiates cue-induced cocaine-seeking in an animal model of relapse
Physiol Behav
Potentiation of cue-induced reinstatement of cocaine-seeking in rats by the anxiogenic drug yohimbine
Behav Brain Res
Noradrenergic transmission in the extended amygdala: Role in increased drug-seeking and relapse during protracted drug abstinence
Brain Struct Funct
Pathways to relapse: The neurobiology of drug- and stress-induced relapse to drug-taking
J Psychiatry Neurosci
Role of alpha-2 adrenoceptors in stress-induced reinstatement of alcohol seeking and alcohol self-administration in rats
Psychopharmacology (Berl)
Clonidine blocks stress-induced reinstatement of heroin seeking in rats: An effect independent of locus coeruleus noradrenergic neurons
Eur J Neurosci
The role of corticotropin-releasing factor and corticosterone in stress- and cocaine-induced relapse to cocaine seeking in rats
J Neurosci
The role of corticotrophin-releasing factor in stress-induced relapse to alcohol-seeking behavior in rats
Psychopharmacology (Berl)
CP-154,526, a selective, non-peptide antagonist of the corticotropin-releasing factor1 receptor attenuates stress-induced relapse to drug seeking in cocaine- and heroin-trained rats
Psychopharmacology (Berl)
Corticotropin-releasing factor, but not corticosterone, is involved in stress-induced relapse to heroin-seeking in rats
J Neurosci
Hypothalamic-pituitary-adrenal axis and sympatho-adreno-medullary responses during stress-induced and drug cue-induced cocaine craving states
Psychopharmacology (Berl)
Potential role for the hypothalamo-pituitary-adrenal axis in the conditioned reinforcer-induced reinstatement of extinguished cocaine seeking in rats
Psychopharmacology (Berl)
Ketoconazole blocks the stress-induced reinstatement of cocaine-seeking behavior in rats: Relationship to the discriminative stimulus effects of cocaine
Psychopharmacology (Berl)
Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: Preliminary findings
Psychopharmacology (Berl)
Clonidine blocks stress-induced craving in cocaine users
Psychopharmacology
Cited by (64)
Alpha<inf>1</inf>-adrenergic receptor blockade in the ventral tegmental area modulates conditional stimulus-induced cocaine seeking
2019, NeuropharmacologyCitation Excerpt :Interestingly, both cocaine-associated CSs and stress during cocaine abstinence evoke similar responses, such as increased anxiety, heart rate, systolic blood pressure, activation of the sympathoadrenomedullar system and release of the stress hormones (Sinha et al., 2003). Increased noradrenaline (NA) signaling in the central nervous system accompany these changes, as several adrenergic receptor (AR) ligands have been demonstrated to alleviate cocaine craving in humans (Jobes et al., 2011; Sinha et al., 2007; Fox and Sinha, 2014; Shorter et al., 2013) and rats (Solecki et al., 2018; Zhang and Kosten, 2005; Smith and Aston-Jones, 2011). These studies have indicated the utility of pharmacological manipulation of NAergic signaling in cocaine use disorder but lack clear evidence of the locus of the relevant brain mechanisms.
Modeling cocaine relapse in rodents: Behavioral considerations and circuit mechanisms
2018, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :In rats, cues activate the hypothalamic-pituitary-adrenal axis and induce anxiety-like behavior (DeVries et al., 1998; DeVries and Pert, 1998), and reinstatement of cocaine seeking elicited by footshock or yohimbine is observed primarily when response-contingent cues are also present (Chen et al., 2015; Feltenstein and See, 2006). Furthermore, stress-related systems like NE and CRF are required for rodent cued reinstatement, as reducing NE release with alpha-2 receptor stimulation, and antagonism or knockdown of CRF1 receptors, blocks psychostimulant seeking elicited by cues (Chen et al., 2014; Moffett and Goeders, 2007; Smith and Aston-Jones, 2011). CRF in insular cortex, a region associated with addiction-related craving in humans (Naqvi et al., 2007), is also required for cue-induced seeking (Cosme et al., 2015).
Medications for alcohol use disorders: An overview
2018, Pharmacology and TherapeuticsThe Role of Norepinephrine in Drug Addiction: Past, Present, and Future
2018, Neural Mechanisms of Addiction