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Michael T Bardo

Publications and source records attributed to Michael T Bardo.

25 records · Page 2Linked to original sources
PubMed2003

Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats.

Lobeline inhibits [3H]nicotine binding to rat brain membranes and nicotine-induced [3H]dopamine release from superfused rat striatal slices, indicating that lobeline acts as a nicotinic receptor antagonist. To determine whether lobeline also inhibits the effects of nicotine in vivo, the present study assessed the effect of lobeline pretreatment on nicotine-induced hyperactivity and sensitization. For 12 consecutive days, rats were injected subcutaneously with lobeline (3 mg/kg) or saline, followed 10 min later by nicotine (0.3 mg/kg) or saline injection, and activity was monitored. To determine if lobeline inhibits induction of sensitization to nicotine, 1 or 28 days later, rats were pretreated with saline followed by nicotine or saline. Lobeline attenuated nicotine-induced hyperactivity when both drugs were administered repeatedly. Although an initial injection of lobeline produced hypoactivity, tolerance to this effect developed. Importantly, tolerance did not develop to the lobeline-induced attenuation of nicotine hyperactivity. Lobeline attenuated the induction of sensitization to nicotine 1 day, but not 28 days, after the cessation of lobeline treatment. These results demonstrate that systemic administration of lobeline attenuates the locomotor-activating effects of repeated nicotine injection and the sensitization to nicotine, consistent with lobeline inhibition of nicotinic receptors and/or neurotransmitter transporters.

Animals↗
PubMed2002

Lobeline does not serve as a reinforcer in rats.

RATIONALE: Previous results demonstrated that pretreatment with lobeline attenuates d-methamphetamine self-administration in rats. OBJECTIVE: The present experiments determined if lobeline serves as a reinforcer, if it decreases d-methamphetamine-induced reinstatement of d-methamphetamine self-administration, and if it activates the mesolimbic and nigrostriatal dopamine (DA) pathways in Sprague-Dawley male rats. METHODS: The ability of intravenous (IV) lobeline (0.015-0.15 mg/kg per infusion) to engender responding and the ability of lobeline (0.015 and 0.05 mg/kg per infusion) to substitute for d-methamphetamine was determined using the self-administration paradigm. Experiments were also performed to determine if lobeline (1.0 and 3.0 mg/kg) reinstates responding for d-methamphetamine or alters the ability of d-methamphetamine (1.0 mg/kg per infusion) to reinstate responding following extinction. The effect of lobeline (3.0 mg/kg) or d-methamphetamine (1.0 and 3.0 mg/kg) on DA and dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens and striatum were also determined. RESULTS: Lobeline was not self-administered and did not substitute for d-methamphetamine. Also, lobeline did not reinstate responding for d-methamphetamine following extinction nor did it alter d-methamphetamine-induced reinstatement. Furthermore, lobeline did not alter DA or DOPAC levels in the either the nucleus accumbens or striatum. CONCLUSIONS: Taken together, the present results indicate that lobeline decreases d-methamphetamine self-administration by decreasing reward, not by acting as a substitute reinforcer.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2002

Effects of opioid antagonists on unconditioned and conditioned hyperactivity to morphine.

In a series of experiments, the ability of selective mu- (beta-funaltrexamine, beta-FNA), delta- (naltrindole, nalt) and kappa- (nor-binaltorphimine, nor-BNI) opioid receptor antagonists to attenuate the unconditioned and conditioned hyperactive effects of morphine was examined. For comparison, the nonselective opioid receptor antagonist naloxone (nalx) was also examined. Locomotor activity served as the behavioral measure. Experiment 1 found that doses of 1 and 4, but not 16 mg/kg, of morphine effectively produced conditioned hyperactivity (CH). Experiments 2a-d found that beta-FNA, nalt, nor-BNI and nalx, respectively, attenuated unconditioned morphine-induced hyperactivity. Experiments 3a-c, however, found that none of the selective antagonists, given individually, attenuated CH. In contrast, nalx did attenuate CH (Experiment 3d). Collectively results suggest that the unconditioned and conditioned hyperactive responses to morphine are mediated by different receptor systems and that activation of multiple opioid-receptor subtypes mediate expression of CH.

Analgesics, Opioid↗
PubMed2002

On the nature of the conditioned stimulus: comment on Leri and Stewart (2002).

F. Leri and J. Stewart (2002) present convincing evidence that a relapse to heroin-seeking behavior is established when rats are given a momentary lapse in which they are allowed to respond while under the influence of heroin. Although exposure to a conditioned stimulus (CS) paired with heroin self-infusion did not induce a relapse, it was able to control responding. In addition to serving as both a discriminative stimulus and a conditioned reinforcer, it is argued in this article that the CS also may have positive hedonic value independent of its association with heroin and that this property should be considered in interpreting the results of future experiments.

Animals↗
PubMed2002

Reboxetine: attenuation of intravenous nicotine self-administration in rats.

The ability of reboxetine, a selective inhibitor of the norepinephrine transporter and noncompetitive antagonist at neuronal nicotinic receptors, to alter nicotine self-administration in rats was compared with that of mecamylamine, a classical noncompetitive antagonist at nicotinic receptors. The ability of reboxetine to alter sucrose-maintained responding was also examined to assess the specificity of the effect on nicotine self-administration. Rats were trained on a fixed ratio 5 schedule to self-administer nicotine (0.02 mg/kg/infusion i.v.) or to respond for sucrose pellets. Upon reaching a stable baseline, rats were pretreated 15 min before the session with vehicle, reboxetine (racemic), (+)-(S,S)-reboxetine (0.3-30 mg/kg s.c.) or mecamylamine (0.5-4 mg/kg s.c). To assess the effect of repeated administration, reboxetine (5.6 mg/kg) was injected once daily for 14 consecutive sessions before either nicotine self-administration or sucrose-maintained responding. Specificity was further assessed by examining the ability of repeated administration of reboxetine (5.6 mg/kg) to alter nicotine-induced hyperactivity (0.8 mg/kg). Reboxetine, (+)-(S,S)-reboxetine, and mecamylamine dose dependently decreased nicotine self-administration by ~60%, whereas reboxetine and (+)-(S,S)-reboxetine decreased sucrose-maintained responding to a lesser extent (~20%). Repeated administration of reboxetine (5.6 mg/kg) decreased nicotine self-administration and sucrose-maintained responding across the 14 sessions, suggesting that tolerance did not develop to these effects of reboxetine. Additionally, reboxetine did not alter baseline locomotor activity, indicating that the decrease in operant responding for nicotine and sucrose was not the result of a nonspecific decrease in activity. The reboxetine-induced decrease in nicotine self-administration and sucrose-maintained responding may be the result of inhibition of norepinephrine transporters and/or neuronal nicotinic receptor function.

Adrenergic Uptake Inhibitors↗
PubMedDate not supplied

Review of the pharmacology and clinical profile of bupropion, an antidepressant and tobacco use cessation agent.

Bupropion hydrochloride ((+/-)-2-tert-butylamino)-3'-chloropropiophenone x HCl) is a nonselective inhibitor of the dopamine transporter (DAT) and the norepinephrine transporter (NET) and is also an antagonist at neuronal nicotinic acetylcholine receptors (nAChRs). In animal models used commonly to screen for antidepressant activity, bupropion shows a positive response. Also using animal models, bupropion has been shown to attenuate nicotine-induced unconditioned behaviors, to share or enhance discriminative stimulus properties of nicotine and to have a complex effect on nicotine self-administration, i.e., low doses augmenting nicotine self-administration and high doses attenuating self-administration. Current studies show that bupropion facilitates the acquisition of nicotine conditioned place preference in rats, further suggesting that bupropion enhances the rewarding properties of nicotine. Bupropion has been shown to attenuate the expression of nicotine withdrawal symptoms in both animal models and human subjects. With respect to relapse, current studies show that bupropion attenuates nicotine-induced reinstatement in rats, but large individual differences are apparent. Clinically, bupropion is used as a treatment for two indications, as an antidepressant, the indication for which it was developed, and as a tobacco use cessation agent. In clinical trials, bupropion is being tested as a candidate treatment for psychostimulant drug abuse, attention-deficit hyperactivity disorder (ADHD) and obesity. Bupropion is available in three bioequivalent oral formulations, immediate release (IR), sustained release (SR), and extended release (XL). Extensive hepatic metabolism of bupropion produces three pharmacologically active metabolites, which may contribute to its clinical profile.

Animals↗