Biomedical subjects

M T Bardo

Publications and source records attributed to M T Bardo.

At least 19 recordsLinked to original sources

PubMed2006

Effects of nornicotine enantiomers on intravenous S(-)-nicotine self-administration and cardiovascular function in rats.

RATIONALE: Previous neurochemical evidence indicates that R(+)-nornicotine is more potent than S(-)-nornicotine in evoking dopamine release in rat nucleus accumbens slices. OBJECTIVE: The current study tested the hypothesis that R(+)-nornicotine is also more potent than S(-)-nornicotine in selectively decreasing intravenous S(-)-nicotine self-administration in rats. RESULTS: After acute pretreatment (1-10 mg/kg for each enantiomer), R(+)-nornicotine was more potent than S(-)-nornicotine in decreasing S(-)-nicotine self-administration; in contrast, within the same dose range, the nornicotine enantiomers were equipotent in decreasing sucrose-maintained responding. This enantioselectivity does not likely reflect a difference in bioavailability, since similar levels of nornicotine were recovered from the brain 60 min after injection (5.6 mg/kg for each enantiomer). With repeated pretreatment, tolerance did not develop to the rate-decreasing effect of either nornicotine enantiomer (3 or 5.6 mg/kg) with respect to the decrease in S(-)-nicotine self-administration, although the enantioselectivity dissipated across repeated pretreatments. While both enantiomers acutely produced a similar increase in blood pressure and heart rate, tolerance developed to the blood pressure effects of R(+)-nornicotine, but not to the effects of S(-)-nornicotine, across repeated treatments. CONCLUSION: Both R(+)- and S(-)-nornicotine may have potential utility as a novel tobacco use cessation agent.

Animals↗

PubMed2006

Effect of amphetamine on response inhibition in rats showing high or low response to novelty.

Previous work has shown that rats categorized as either high responder (HR) or low responder (LR) based on the amount of activity assessed in a novel environment show a differential response to stimulant reward, with HR rats self-administering more amphetamine and cocaine than LR rats. The current study assessed behavioral inhibitory processes in HR and LR rats using either fixed consecutive number (FCN) or differential reinforcement of low rate of responding (DRL) tasks. Individual differences in free-choice preference for a novel environment or novel object were also assessed to determine if these measures were predictive of performance on these inhibitory tasks. Results showed that, regardless of the test used to characterize individual differences in response to novelty, groups showed a similar ability to learn the FCN and DRL tasks. When subsequently pretreated with amphetamine, there was no significant difference between groups in performance efficiency (accuracy) on either the FCN or DRL task; however, based on activity in inescapable novelty, HR rats were less sensitive than LR rats to amphetamine-disrupted responding on the reinforcement lever in the FCN task. Although a deficit in inhibition is generally thought to play a role in drug abuse behavior, the differential rate of stimulant self-administration described previously between HR and LR rats more likely reflects an incentive motivational effect that is independent of response inhibition.

Amphetamines↗

PubMed2006

Age and sex differences in the locomotor effect of repeated methylphenidate in rats classified as high or low novelty responders.

RATIONALE: Rats displaying high levels of activity in an inescapable novel environment (high responders; HR) are more sensitive to the locomotor effect of stimulant drugs than rats displaying low levels of activity (low responders; LR). OBJECTIVE: The current study determined the age- and sex-dependent locomotor effects of repeated methylphenidate in HR and LR rats. MATERIALS AND METHODS: Periadolescent and adult male and female Sprague-Dawley rats were first classified as HR or LR; rats were also classified as high or low novelty seekers based on free-choice preference for a novel environment. Locomotor activity was subsequently assessed after ten daily injections of methylphenidate (3 or 10 mg/kg s.c.) or saline. Fifteen days later, rats were challenged with saline and methylphenidate (10 mg/kg) over 2 days. RESULTS: During the repeated methylphenidate treatment phase, adult females showed greater methylphenidate-induced hyperactivity than adult males; there was no reliable difference in methylphenidate-induced hyperactivity between HR and LR rats of either age or sex. However, periadolescent male HR rats given repeated methylphenidate showed greater conditioned hyperactivity after the saline challenge than periadolescent male LR rats. Further, adult female HR rats given repeated methylphenidate showed greater conditioned hyperactivity and sensitization than adult female LR rats. In contrast, although free-choice novelty preference was greater among periadolescents than adults, individual differences in this variable did not predict the effect of repeated methylphenidate during any phase of the experiment. CONCLUSION: Although individual differences in response to inescapable novelty predict methylphenidate-induced conditioned hyperactivity and sensitization, this relationship is moderated by age and sex.

Age Factors↗

PubMed2005

Contribution of dihydro-beta-erythroidine sensitive nicotinic acetylcholine receptors in the ventral tegmental area to cocaine-induced behavioral sensitization in rats.

Nicotinic acetylcholine receptors (nAChRs) are known to play a role in several aspects of cocaine addiction. Recently, systemic administration of the nicotinic receptor antagonist mecamylamine was shown to block the induction of long-term locomotor sensitization to cocaine. Behavioral sensitization being a model of long-term neuroadaptations to chronic cocaine exposure, the goal of the current study was to identify the anatomical localization, as well as the nature, of the nicotinic receptors involved. Male Sprague-Dawley rats were stereotaxically implanted with bilateral cannula into either the ventral tegmental area (VTA) or the nucleus accumbens (Nacc). On each of the six consecutive days, rats were microinjected bilaterally with the selective nicotinic antagonists dihydro-beta-erythroidine (DHbetaE), methyllycaconitine (MLA) or saline, followed by an intra-peritoneal injection of cocaine (15 mg/kg, i.p.) or saline. Following a 2-week withdrawal period, rats received a final injection of cocaine in the absence of nicotinic antagonist to test for sensitization. When microinjected into the VTA, DHbetaE, but not MLA, prevented the induction of behavioral sensitization to cocaine. In contrast, behavioral sensitization was present in rats receiving DHbetaE microinjections into the Nacc. Neither antagonist, whether injected into the VTA or the Nacc had any significant effect on the acute locomotor response to cocaine. Given the subtype selectivity of the nicotinic antagonists employed, heteromeric beta2-containing (beta2*) nAChRs, but not homomeric alpha7* nAChRs, in the VTA may be involved in the neuroadaptive changes underlying cocaine sensitization.

Aconitine↗

PubMed2005

Effect of a novel nicotinic receptor antagonist, N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide, on nicotine self-administration and hyperactivity in rats.

RATIONALE AND OBJECTIVE: Recent work has shown that the novel compound N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB) may selectively block nicotinic acetylcholine receptors involved in regulating dopamine release. The current experiments examined the acute effect of bPiDDB on nicotine self-administration, sucrose-maintained responding, and nicotine-induced changes in acute and sensitized locomotor activity. METHODS: Rats were first trained to respond for either nicotine (i.v.) or sucrose pellets using a standard two-lever operant conditioning procedure using a fixed ratio 5 schedule of reinforcement and were then pretreated with bPiDDB (0, 0.3, 1, or 3 mg kg(-1)) 15 min prior to the session. In separate experiments, rats were assessed for nicotine-induced changes in locomotor activity following pretreatment with bPiDDB (1 or 3 mg kg(-1)) or mecamylamine (1 mg kg(-1)); pretreatments were assessed with both acute and repeated nicotine (0.4 mg kg(-1)) treatment. RESULTS: Results showed that bPiDDB dose-dependently decreased nicotine self-administration, but not sucrose-maintained responding. In the locomotor experiments, bPiDDB attenuated the hyperactivity produced by acute and repeated nicotine; however, this effect was not robust compared to mecamylamine. In contrast to mecamylamine, bPiDDB did not block the initial hypoactivity produced by acute nicotine. CONCLUSION: Since bPiDDB decreased nicotine self-administration specifically, this novel nicotinic receptor antagonist may constitute a lead for the development of a clinically useful treatment for tobacco dependence.

Animals↗

PubMed2004

Lobeline produces conditioned taste avoidance in rats.

Previous results indicate that pretreatment with lobeline attenuates methamphetamine (METH) self-administration in rats, but not by acting as a substitute reinforcer. Given these findings, it has been suggested that lobeline may serve as a useful pharmacotherapy for psychostimulant abuse. However, because lobeline produces emesis and nausea in humans, the present study examined whether lobeline has direct effects on taste avoidance behavior in rats within the same dose range shown previously to decrease METH self-administration. Two experiments utilized a Pavlovian conditioning procedure to determine if lobeline produces conditioned taste avoidance (CTA) in rats. In Experiments 1 and 2, rats consumed either novel milk or salt solutions, respectively, and within 10 min, were injected with lobeline (0.3-3.0 mg/kg) or METH (0.3-3.0 mg/kg). A single-bottle test conducted 48 h after flavor-drug pairings indicated that the dose of lobeline that reduced METH self-administration in a previous study (i.e., 3.0 mg/kg) also produced reliable CTA for milk and salt solution. These findings suggest a need to develop lobeline analogs that reduce METH self-administration, but do not produce CTA following the consumption of a novel solution.

Animals↗

PubMed2003

The effect of neurotoxic doses of methamphetamine on methamphetamine-conditioned place preference in rats.

RATIONALE: Methamphetamine has been shown to produce neurotoxicity demonstrated by depletions of dopamine and serotonin in the striatum and nucleus accumbens. OBJECTIVE: The current study examined the effects of neurotoxic doses of methamphetamine on the rewarding effect of subsequent administration of methamphetamine assessed by the conditioned place preference (CPP) procedure. METHODS: Male and female rats were treated with a neurotoxic regimen of methamphetamine (4 x 10 mg/kg, s.c., once every 2 h) or saline, and concentrations of dopamine, 3,4-dihydroxyphenylacetic acid, serotonin, and 5-hydroxyindoleacetic acid were measured 15 days later in the striatum, nucleus accumbens, and prefrontal cortex (PFC). In another experiment, male rats were given methamphetamine neurotoxic treatment or saline and were then conditioned 7 days later with methamphetamine (0.1, 0.3, or 1.0 mg/kg, s.c.) or saline using a four-trial CPP procedure. Locomotor activity was also measured during the conditioning sessions to investigate whether or not the neurotoxic methamphetamine treatment altered locomotor activity following a subsequent methamphetamine challenge. RESULTS: Males and females did not differ significantly in the amount of neurochemical depletion produced by methamphetamine in any brain region. Collapsed across sex, dopamine was significantly depleted in nucleus accumbens (25%) and striatum (51%); serotonin was significantly depleted in nucleus accumbens (35%), striatum (34%) and PFC (33%). The methamphetamine challenge dose dependently increased locomotor activity, but the increase was not affected by treatment with neurotoxic doses of methamphetamine. In contrast, treatment with neurotoxic doses of methamphetamine enhanced CPP at the intermediate conditioning dose (0.3 mg/kg). CONCLUSIONS: These results indicate that the rewarding effect of methamphetamine is enhanced by prior treatment with neurotoxic doses of methamphetamine, suggesting either a compensatory hyperfunctioning of spared dopamine neurons or a loss of inhibitory control from serotonergic input.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2003

Effects of beta-funaltrexamine and naloxonazine on single-trial morphine-conditioned place preference and locomotor activity.

The current study assessed the ability of the selective irreversible mu-opioid receptor antagonists beta-funaltrexamine (betaFNA) and naloxonazine (NALZ) to alter the locomotor and rewarding effects of a single intravenous injection of morphine using the conditioned place preference (CPP) model. In the first experiment, rats were conditioned with a single injection of morphine (10 mg/kg iv) paired with one compartment of a CPP apparatus and then were tested for CPP at either 1 or 7 days after conditioning. Rats showed hypoactivity following acute morphine on the conditioning trial and showed CPP when tested either 1 or 7 days later. In the next experiments, rats were pretreated with betaFNA (20 mg/kg sc, 20 h before conditioning), NALZ (15 or 30 mg/kg sc, 24 h before conditioning) or saline and then were conditioned with a single injection of morphine (10 mg/kg iv) or saline. Pretreatment with NALZ alone, but not betaFNA, significantly decreased locomotor activity; neither antagonist alone produced a significant shift in preference for either compartment of the CPP apparatus. Pretreatment with either betaFNA or NALZ blocked completely morphine-induced hypoactivity, but neither antagonist had a significant effect on morphine CPP. These results indicate that mu-opioid receptors are more critically involved in acute morphine-induced hypoactivity than in acute morphine reward.

Animals↗

PubMed2002

Environmental enrichment decreases intravenous amphetamine self-administration in rats: dose-response functions for fixed- and progressive-ratio schedules.

RATIONALE: Although environmental enrichment renders rats more sensitive to the neurobehavioral effects of acute amphetamine, a previous study found that enriched rats self-administer less amphetamine than isolated rats at a low unit dose (0.03 mg/kg per infusion). In that study, however, acquisition of self-administration was limited to only two amphetamine unit doses using a fixed ratio (FR) schedule. OBJECTIVE: The current study defined the full dose-response relationship for amphetamine self-administration under FR1 and progressive ratio (PR) schedules of reinforcement in rats raised in either an enriched condition (EC) or an isolated condition (IC). METHODS: Rats were raised from 21 to 50 days of age in either an EC or IC environment. Rats were then trained to press a lever for sucrose before implantation of an intravenous jugular catheter. After implantation of the catheter, rats were allowed to acquire stable response patterns under an FR1 or PR schedule of reinforcement before determination of the dose-response function.RESULTS. EC rats self-administered less amphetamine at a low unit dose under both FR1 (0.006 mg/kg per infusion) and PR (0.02 mg/kg per infusion) schedules. However, responding for high unit doses was similar between the two groups. CONCLUSIONS: This result suggests that environmental enrichment may be a protective factor for reducing amphetamine intake at a low dose.

Amphetamine↗

PubMed2002

Locomotor stimulant effects of nornicotine: role of dopamine.

Nornicotine (NORNIC) is a tobacco alkaloid and behaviorally active nicotine metabolite in vivo. Previous behavioral research has shown that NORNIC has locomotor stimulant and reinforcing effects in rats similar to that of nicotine. Results from the current study showed that a bilateral lesion of the nucleus accumbens decreased the locomotor stimulant effect of NORNIC across repeated injections. Pretreatment with the dopamine (DA) D1 receptor antagonist SCH23390 did not block the locomotor stimulant effect of NORNIC or the initiation of sensitization following repeated NORNIC administration. The D2 receptor antagonist eticlopride, however, blocked both the stimulant effect and the initiation of sensitization following repeated NORNIC. Additionally, NORNIC was found to increase synthesis and metabolism of DA, with a greater effect in the mesolimbic pathway compared to the nigrostriatal pathway. Taken together, these results suggest that expression of NORNIC-induced locomotor activity is dependent upon ascending dopaminergic mesolimbic projections, providing additional evidence that NORNIC plays a contributory role in tobacco dependence.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2001

Contributory role for nornicotine in nicotine neuropharmacology: nornicotine-evoked [3H]dopamine overflow from rat nucleus accumbens slices.

Nornicotine is a tobacco alkaloid and an active nicotine metabolite, which accumulates in brain to pharmacologically relevant concentrations following repeated nicotine administration to rats. Furthermore, nornicotine is self-administered by rats, indicating that it has reinforcing efficacy and may contribute to nicotine dependence. Since drugs of abuse activate the mesolimbic dopamine (DA) system to produce rewarding effects, the present study tested the hypothesis that nornicotine evokes DA release from nucleus accumbens in a nicotinic receptor-mediated manner. Rat nucleus accumbens slices were preloaded with [3H]DA and superfused for 60 min in the absence and presence of a range of alkaloid concentrations. Superfusate samples were collected and alkaloid-evoked [3H]overflow was determined. S(-)-Nornicotine (EC(50) value = 3.0 microM), R(+)-nornicotine (EC(50) value = 0.48 microM), and S(-)-nicotine (EC(50) value = 70 nM) evoked [3H]overflow in a concentration-dependent manner. For each nornicotine enantiomer, 0.3 microM was the lowest concentration to evoke significant [3H]overflow. Dihydro-beta-erythroidine (DHbetaE, 10 microM), a classical nicotinic receptor antagonist, inhibited the S(-)-nornicotine-evoked [3H]overflow, indicating the involvement of nicotinic receptors. Furthermore, the effect of S(-)-nornicotine was calcium-dependent, consistent with a nicotinic receptor-mediated mechanism. Whereas S(-)-nornicotine was found previously to be more potent in the striatum, R(+)-nornicotine was more potent than its enantiomer in nucleus accumbens, suggesting the involvement of different nicotinic receptor subtypes in these brain regions. Thus, the results of the current study indicate that nornicotine stimulated DA release from nucleus accumbens in a nicotinic receptor-mediated manner, further supporting the hypothesis that nornicotine contributes to tobacco dependence.

Analysis of Variance↗

PubMed2001

Effect of 6-hydroxydopamine or repeated amphetamine treatment on mesencephalic mRNA levels for AMPA glutamate receptor subunits in the rat.

Expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) subunit mRNAs were assayed in the ventral mesencephalon of rats that received either a unilateral microinjection of the dopamine neurotoxin 6-hydroxydopamine (6-OHDA; Experiment 1) or repeated treatment with amphetamine (Experiment 2). GluR2 levels were decreased 1 and 3 days after the lesion, and GluR1 and GluR3 levels also showed a transient decrease at 1 day after the lesion. Repeated amphetamine treatment did not significantly alter GluR1-4 levels measured 30 min after the third or tenth amphetamine injection, even though locomotor sensitization was obtained. Thus, while the present results indicate that AMPA receptor subunits are associated with dopamine-containing cell bodies in the ventral mesencephalon, these transcripts may not be responsible for the development of amphetamine sensitization.

Adrenergic Agents↗

PubMed2001

Environmental enrichment decreases intravenous self-administration of amphetamine in female and male rats.

RATIONALE: Previous work has shown that environmental enrichment alters amphetamine-induced locomotor activity and conditioned place preference. OBJECTIVE: The present study examined the effect of environmental enrichment on amphetamine self-administration. METHODS: Female and male rats were raised from 21 days of age in one of three different conditions: an enriched condition (EC) containing novel objects and social partners, a social condition (SC) containing social partners only, or an isolated conditioned (IC) without objects or social partners. Beginning at 51 days of age, rats were then tested for operant responding for a sucrose reinforcer using an incremental fixed ratio (FR) requirement across four sessions. Rats were then implanted with a chronic indwelling intravenous catheter and were allowed to self-administer amphetamine (0.03 or 0.1 mg/kg per infusion) for five FR1 sessions, followed by a progressive ratio (PR) session. RESULTS: EC rats initially showed an increase in sucrose-reinforced responding relative to IC rats and this environment-induced difference was greater in females than in males. However, in both sexes, the environment-induced difference in sucrose-reinforced responding dissipated completely across repeated sessions. With amphetamine self-administration, both EC and SC rats earned fewer infusions than IC rats across repeated FRI sessions using the low dose of amphetamine (0.03 mg/kg per infusion), but not using the higher dose of amphetamine (0.1 mg/kg per infusion). EC rats also earned fewer self-infusions of the low amphetamine dose on the PR session relative to IC rats. The effects of environmental enrichment on amphetamine self-administration were similar in both females and males. CONCLUSION: These results suggest that environmental enrichment may serve as a protective factor for reducing amphetamine self-administration.

Amphetamine↗

PubMed2001

Once weekly administration of nicotine produces long-lasting locomotor sensitization in rats via a nicotinic receptor-mediated mechanism.

RATIONALE: Chronic nicotine administration results in dynamic changes in neuronal function, expressed as behavioral sensitization in animals and addiction in smokers. OBJECTIVES: The present study was undertaken to determine whether once-weekly nicotine injection produces sensitization to the locomotor-activating properties of nicotine as a result of nicotinic receptor activation. METHODS: Once weekly for 6 weeks, rats were administered (s.c.) two saline injections or saline and nicotine (0.35 mg/kg), and locomotor activity was monitored. Rats remained in the home cage for 21 days, and subsequently were injected with the appropriate treatment to determine whether sensitization persisted. Rats were also injected with saline or mecamylamine (1.2 mg/kg) followed by saline or nicotine once weekly for 6 weeks to determine the effect of mecamylamine and whether it inhibited nicotine-induced hyperactivity. A separate group was injected with saline and nicotine once weekly for 4 weeks; on week 5, mecamylamine and nicotine were administered to determine whether mecamylamine inhibited the expression of sensitization. Separate groups were injected with mecamylamine and nicotine once weekly for 5 weeks or 6 weeks; on week 6 or week 9, respectively, saline and nicotine were injected to determine whether mecamylamine inhibited the initiation of sensitization. RESULTS: Sensitization to the locomotor-activating properties of nicotine developed following four nicotine injections across a 28-day period and persisted following 21 days of no drug treatment. Mecamylamine did not alter activity but attenuated both the initiation and expression of sensitization. CONCLUSIONS: Nicotinic receptor activation following once-weekly nicotine administration produces long-lasting behavioral sensitization, suggesting that even infrequent nicotine exposure initiates neuroadaptive processes associated with nicotine addiction.

Animals↗

PubMed2001

Dopamine D3 receptors are involved in amphetamine-induced contralateral rotation in 6-OHDA lesioned rats.

The aim of the present experiment was to investigate the possibility that alterations in dopamine D3 receptors have a role in the normalization of function that occurs following a unilateral lesion of the medial forebrain bundle induced by 6-hydroxydopamine (6-OHDA). Unilateral lesions result in an enhanced rotational response to dopamine agonists that appears to be due to an increase in stimulatory D2 receptors on the lesioned side that occurs by about 1 week postlesion. The present experiment assessed the involvement of D3 receptors in rotational behavior by testing the animals at 48 h postlesion. At this time interval, D2 receptors have not become up-regulated. In contrast, D3 receptors have been shown to be down-regulated. Rats with > or = 98% dopamine depletion induced by 6-OHDA exhibited mostly ipsilateral rotation in response to an injection of amphetamine. This rotation was not affected by pretreatment with the D3 antagonist U-99194A. Rats with 80-97% dopamine depletion exhibited mostly contralateral rotation in response to amphetamine and this rotation was blocked by pretreatment with U-99194A. In addition, a decrease in D3 receptor binding was observed by 48 h postlesion. These results support the hypothesis that the decrease in D3 receptors seen following denervation is involved in the compensatory response of the system. This may have important clinical relevance in the treatment of disorders such as Parkinson's disease and drug abuse.

Adrenergic Agents↗

PubMed2001

Individual differences in behavioral responses to novelty and amphetamine self-administration in male and female rats.

Previous work has shown that individual differences in locomotor activity in an inescapable novel environment can predict acquisition of amphetamine self-administration. The current study examined whether individual differences in approach to novelty in a free choice test could also predict amphetamine self-administration. Further, the current study examined whether individual differences in either free choice or inescapable novelty tests could predict responding for a nondrug reinforcer (sucrose) in the presence and absence of amphetamine. Male and female rats were first tested for their response to free choice novelty (playground maze and novelty-induced place preference tests) and inescapable novelty. They were then tested for acquisition of sucrose-reinforced responding, amphetamine-induced changes in maintenance of sucrose-reinforced responding, and amphetamine self-administration. Based on the inescapable novelty test, acquisition of sucrose-reinforced responding was more rapid in male high responders (HR) compared to low responders (LR). This effect in males did not generalize to females. None of the novelty tests predicted the ability of amphetamine to decrease sucrose-maintained responding. However, using the inescapable novelty test, both male and female HRs self-administered more amphetamine than LRs within the dose range tested (0.03-0.16 mg/kg/infusion). Neither the playground maze nor the novelty-induced place preference test predicted amphetamine self-administration. These results indicate that responses to free choice novelty and inescapable novelty predict different components of amphetamine-induced behavior.

Animals↗

PubMed2001

Lobeline attenuates d-methamphetamine self-administration in rats.

alpha-Lobeline inhibits d-amphetamine-evoked dopamine release from striatal slices in vitro, appearing to reduce the cytosolic pool of dopamine available for reverse transport by the dopamine transporter. Based on this neurochemical mechanism of action, the present study determined if lobeline decreases d-methamphetamine self-administration. Rats were surgically implanted with jugular catheters and were trained to lever press on a fixed ratio 5 schedule for intravenous d-methamphetamine (0.05 mg/kg/infusion). To assess the specificity of the effect of lobeline, another group of rats was trained to lever press on a fixed ratio 5 schedule for sucrose reinforcement. Pretreatment of rats with lobeline (0.3-3.0 mg/kg, 15 min prior to the session) decreased responding for both d-methamphetamine and sucrose reinforcement. Following repeated lobeline (3.0 mg/kg) administration, tolerance developed to the decrease in responding for sucrose; however, the lobeline-induced decrease in responding for d-methamphetamine persisted. Furthermore, the lobeline-induced decrease in responding for d-methamphetamine was not surmounted by increasing the unit dose of d-methamphetamine. These results suggest that lobeline produces a nonspecific rate suppressant effect following acute administration, to which tolerance develops following repeated administration. Importantly, the results also suggest that repeated administration of lobeline specifically decreases responding for d-methamphetamine in a noncompetitive manner. Thus, lobeline may be an effective, novel pharmacotherapy for d-methamphetamine abuse.

Amphetamine-Related Disorders↗

PubMed2001

Exposure to novel environmental stimuli decreases amphetamine self-administration in rats.

Researchers examined whether exposure to novel environmental stimuli reduces drug self-administration. Rats were trained to self-administer amphetamine on a fixed ratio (FR) 5 schedule of reinforcement and then were exposed to novel stimuli during the session. Responding was significantly decreased with exposure to novelty but returned to baseline levels on intervening nonexposure sessions. In 2 subsequent experiments, rats were exposed to novel plastic objects prior to the session. Immediately following exposure, rats were allowed to self-administer amphetamine on an FR 1 schedule, which was increased gradually to an FR 5 either using predetermined increments or on the basis of performance criteria. Exposure to the novel objects significantly decreased acquisition of amphetamine self-administration in both situations. Results suggest that exposure to novel environmental stimuli may be effective at reducing drug self-administration.

Amphetamine↗