Stress- and pharmacologically-induced behavioral sensitization increases vulnerability to acquisition of amphetamine self-administration

1990 ◽  
Vol 514 (1) ◽  
pp. 22-26 ◽  
Author(s):  
Pier Vincenzo Piazza ◽  
Jean Marie Deminiere ◽  
Michel le Moal ◽  
Hervé Simon
Keyword(s):  
Behavioral Sensitization ◽  
Self Administration

scholarly journals Does Prenatal Methamphetamine Exposure Induce Sensitization to Drugs in Adulthood?

2017 ◽  
pp. S457-S467 ◽  
Author(s):  
E. MACÚCHOVÁ ◽  
R. ŠLAMBEROVÁ
Keyword(s):  
Infant Development ◽  
Drug Exposure ◽  
Behavioral Sensitization ◽  
Drug Effects ◽  
Mechanisms Of Action ◽  
Prenatal Drug Exposure ◽  
Self Administration ◽  
Psychomotor Activity ◽  
Seeking Behavior ◽  
Reward Pathways

Behavioral sensitization is defined as augmented psychomotor activity, which can be observed after drug re-administration following withdrawal of repeated drug exposure. It has been shown that abuse of one drug can lead to increased sensitivity to certain other drugs. This effect of developed general drug sensitivity is called cross-sensitization and has been reported between drugs with similar as well as different mechanisms of action. There is growing evidence that exposure to drugs in utero not only causes birth defects and delays in infant development, but also impairs the neural reward pathways, in the brains of developing offspring, in such a way that it can increase the tendency for drug addiction later in life. This review summarizes the results of preclinical studies that focused on testing behavioral cross-sensitization, after prenatal methamphetamine exposure, to drugs administered in adulthood, with both similar and different mechanisms of action. Traditionally, behavioral sensitization has been examined using the Open field or the Laboras Test to record locomotor activity, and the Conditioned Place Preference and Self-administration test to examine drug-seeking behavior. However, it seems that prenatal drug exposure can sensitize animals not only to the locomotor-stimulating and conditioning effects of drugs, but may also be responsible for modified responses to various drug effects.

scholarly journals Orexin A role in mechanisms of reinforcement in the bed nucleus of stria terminalis

2015 ◽  
Vol 13 (2) ◽  
pp. 20-26
Author(s):  
Andrei Andreevich Lebedev ◽  
Eugeny Grigorievich Shumilov ◽  
Eugeny Rudolfovich Bychkov ◽  
Vitaly Ivanovich Morozov ◽  
Petr Dmitriyevich Shabanov
Keyword(s):  
Lateral Hypothalamus ◽  
Behavioral Sensitization ◽  
Brain Regions ◽  
Brain Stimulation Reward ◽  
Stria Terminalis ◽  
Self Administration ◽  
Orexin A ◽  
Drug Reinforcement ◽  
Bed Nucleus ◽  
Self Stimulation

The orexin family of hypothalamic neuropeptides has been implicated in reinforcement mechanisms relevant to both food and drug reward. Previous behavioral studies with antagonists at the orexin A-selective receptor OX(1), have demonstrated its involvement in behavioral sensitization, conditioned place-preference, self-administration and reinstatement of drugs abuse. There are dense concentrations of hypocretin receptors, in brain regions implicated in drug reinforcement processes, such as the nucleus accumbens, ventral tegmental area and bed nucleus of the stria terminalis Adult male Wistar rats were implanted the stimulating electrodes to the lateral hypothalamus. Simultaneously, the microcanules were implanted into the BNST to inject the OX(1) receptor antagonist. Rats were trained to perform intracranial self-stimulation. The effects of the OX(1)-selective antagonist SB-408124 on brain stimulation-reward (BSR) were measured. SB-408124 injected into the BNST (1µg/1 µl in volume for each injection.) alone had no effect on self-stimulation of lateral hypothalamus. Amphetamine (1 mg/kg i.p.) potentiated BSR, measured as lowering of BSR threshold and enhancing of BSR frequency. Amphetamine-induced stimulatory effects on intracranial self-stimulation was blocked by injections of SB-408124 into BNST. These data demonstrate that OX(1) play an important role in regulating the reinforcing and reward-enhancing properties of amphetamine and suggest that orexin transmission is likely essential for establishing and maintaining the amphetamine habit in human addicts. However, the observations that OX1 antagonism reduce brain reward and block stress- and cue-induced reinstatement of drug-seeking suggests that this class of compounds may be useful additions to stress-reduction and other behavioral therapies in the treatment of substance abuse disorders.

scholarly journals Mitochondrial function influences expression of methamphetamine-induced behavioral sensitization

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
I. Daphne Calma ◽  
Amanda L. Persons ◽  
T. Celeste Napier
Keyword(s):  
Mitochondrial Function ◽  
Behavioral Sensitization ◽  
High Energy ◽  
Behavioral Changes ◽  
Energy Requirements ◽  
Self Administration ◽  
Methamphetamine Use ◽  
Laboratory Rats ◽  
Mitochondrial Toxin ◽  
Brain Changes

AbstractRepeated methamphetamine use leads to long lasting brain and behavioral changes in humans and laboratory rats. These changes have high energy requirements, implicating a role for mitochondria. We explored whether mitochondrial function underpins behaviors that occur in rats months after stopping methamphetamine self-administration. Accordingly, rats self-administered intravenous methamphetamine for 3 h/day for 14 days. The mitochondrial toxin rotenone was administered as (1 mg/kg/day for 6 days) via an osmotic minipump starting at 0, 14 or 28 days of abstinence abstinence. On abstinence day 61, expression of methamphetamine-induced behavioral sensitization was obtained with an acute methamphetamine challenge in rotenone-free rats. Rotenone impeded the expression of sensitization, with the most robust effects obtained with later abstinence exposure. These findings verified that self-titration of moderate methamphetamine doses results in behavioral (and thus brain) changes that can be revealed months after exposure termination, and that the meth-initiated processes progressed during abstinence so that longer abstinence periods were more susceptible to the consequences of exposure to a mitochondrial toxin.

Relapse to drug and alcohol use: a matter of sensitization

2000 ◽  
Vol 12 (1) ◽  
pp. 5-8 ◽  
Author(s):  
A.N.M. Schoffelmeer ◽  
L.J.M.J. Vanderschuren ◽  
A.H. Mulder ◽  
E.H. Jacobs ◽  
T.J. De Vries
Keyword(s):  
Behavioral Sensitization ◽  
Alcohol Addiction ◽  
Behavioral Effects ◽  
Self Administration ◽  
Behavioral Studies ◽  
Seeking Behavior ◽  
Drug And Alcohol Use ◽  
Biochemical Research ◽  
Drug And Alcohol ◽  
The Brain

SUMMARYRepeated exposure of rats to cocaine, amphetamine, opiates, nicotine and alcohol causes a very long-lasting (months) increase in the behavioral effects of these addictive drugs and drug-associated environmental stimuli (sensitization). This hypersensitivity is associated with persistent changes in the reactivity of neurons of the motivational (mesocorticolim-bic) system in the brain. Using an animal model for relapse, recent studies in our laboratory show that relapse to drug-seeking behavior (following extinction of intravenous cocaine or heroin self-administration) depends on the occurrence of sensitization. Accordingly, sensitization and conditioning seem to be more important for the persistence of drug and alcohol addiction then the occurrence of withdrawal phenomena. Biochemical research on the molecular and cellular basis of behavioral sensitization and behavioral studies on readjustment of stimulus responsiveness in rats, is of great importance for the development of an adequate pharmacotherapy of addiction.

scholarly journals Kappa Opioid Receptor Agonist Mesyl Sal B Attenuates Behavioral Sensitization to Cocaine with Fewer Aversive Side-Effects than Salvinorin A in Rodents

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2602 ◽  
Author(s):  
Bronwyn Kivell ◽  
Kelly Paton ◽  
Nitin Kumar ◽  
Aashish Morani ◽  
Aimee Culverhouse ◽  
...  
Keyword(s):  
Side Effects ◽  
Learning And Memory ◽  
Behavioral Sensitization ◽  
Forced Swim Test ◽  
Salvinorin A ◽  
Self Administration ◽  
Kappa Opioid ◽  
Swim Test ◽  
Forced Swim ◽  
Antinociceptive Effects

The acute activation of kappa opioid receptors (KOPr) produces antinociceptive and anti-cocaine effects, however, their side-effects have limited further clinical development. Mesyl Sal B is a potent and selective KOPr analogue of Salvinorin A (Sal A), a psychoactive natural product isolated from the plant Salvia divinorum. We assessed the antinociceptive, anti-cocaine, and side-effects of Mesyl Sal B. The anti-cocaine effects are evaluated in cocaine-induced hyperactivity and behavioral sensitization to cocaine in male Sprague Dawley rats. Mesyl Sal B was assessed for anhedonia (conditioned taste aversion), aversion (conditioned place aversion), pro-depressive effects (forced swim test), anxiety (elevated plus maze) and learning and memory deficits (novel object recognition). In male B6.SJL mice, the antinociceptive effects were evaluated in warm-water (50 °C) tail withdrawal and intraplantar formaldehyde (2%) assays and the sedative effects measured with the rotarod performance task. Mesyl Sal B (0.3 mg/kg) attenuated cocaine-induced hyperactivity and behavioral sensitization to cocaine without modulating sucrose self-administration and without producing aversion, sedation, anxiety, or learning and memory impairment in rats. However, increased immobility was observed in the forced swim test indicating pro-depressive effects. Mesyl Sal B was not as potent as Sal A at reducing pain in the antinociceptive assays. In conclusion, Mesyl Sal B possesses anti-cocaine effects, is longer acting in vivo and has fewer side-effects when compared to Sal A, however, the antinociceptive effects are limited.

P-62DOES SUSCEPTIBILITY TO ALCOHOL BEHAVIORAL SENSITIZATION ALTER OPERANT SELF-ADMINISTRATION AND MOTIVATION FOR ALCOHOL?

2015 ◽  
Vol 50 (suppl 1) ◽  
pp. i61.1-i61
Author(s):  
F. Coune ◽  
M. C. Gonzalez Marin ◽  
M. Naassila ◽  
J. Jeanblanc
Keyword(s):  
Behavioral Sensitization ◽  
Self Administration
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