Does Prenatal Methamphetamine Exposure Induce Sensitization to Drugs in Adulthood?

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.

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Accumbal Neural Responses During the Initiation and Maintenance of Intravenous Cocaine Self-Administration

Journal of Neurophysiology ◽

10.1152/jn.00638.2003 ◽

2004 ◽

Vol 91 (1) ◽

pp. 314-323 ◽

Cited By ~ 32

Author(s):

Laura L. Peoples ◽

Kevin G. Lynch ◽

Jamie Lesnock ◽

Nidhi Gangadhar

Keyword(s):

Drug Effects ◽

Extracellular Recording ◽

Neural Responses ◽

Self Administration ◽

Drug Seeking ◽

Recording Session ◽

Seeking Behavior ◽

Excitatory Responses ◽

Drug Free ◽

Intravenous Cocaine

During a chronic extracellular recording session, animals with a history of cocaine self-administration were allowed to initiate drug seeking under drug-free conditions. Later, in the same recording session, animals engaged in intravenous cocaine self-administration. During the drug-free period, 31% of 70 accumbal neurons showed a significant increase in average firing rate in association with either or both the exposure to cues that signaled the onset of cocaine availability and the subsequent onset of drug-seeking behavior. The neurons that showed an average excitatory response during the drug-free period were the only group of neurons that showed an average excitatory phasic response to cocaine-reinforced lever presses during the drug self-administration session. A majority of the neurons that were activated during the drug-free period, like the majority of other neurons, showed decreases in average firing in response to self-administered cocaine. However, the neurons that were activated during the drug-free period maintained a higher rate of firing throughout the self-administration session than did other accumbal neurons. The data of the present study are consistent with the conclusion that accumbal neurons contribute to, or otherwise process, initiation of drug seeking under drug-free conditions and that they do so via primarily excitatory responses. Furthermore, there is continuity between the drug-free and -exposed conditions in neural responses associated with drug seeking. Finally, the data have potential implications for understanding mechanisms that transduce accumbal-mediated drug effects that contribute to drug addiction.

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The Effects of HIV on Cognitive and Motor Development in Children Born to HIV-Seropositive Women With No Reported Drug Use: Birth to 24 Months

PEDIATRICS ◽

10.1542/peds.96.6.1078 ◽

1995 ◽

Vol 96 (6) ◽

pp. 1078-1082

Author(s):

Caryl L. Gay ◽

F. Daniel Armstrong ◽

Donna Cohen ◽

Shenghan Lai ◽

Marjorie D. Hardy ◽

...

Keyword(s):

Motor Development ◽

Infant Development ◽

Drug Exposure ◽

Maternal Separation ◽

Prenatal Drug Exposure ◽

Control Group ◽

Motor Functioning ◽

Immunodeficiency Virus ◽

The Mean ◽

Hiv Seropositive

Objective. This study documents delays in the mental and motor functioning of infants perinatally infected with human immunodeficiency virus (HIV) while controlling for confounding effects of prenatal drug exposure, ethnicity, socioeconomic status, and maternal separation and death. Methods. The cognitive and motor development of 126 infants born to nondrug-using, HIV-seropositive Haitian women was assessed at 3-month intervals through 24 months of age using the Bayley Scales of Infant Development. By 18 months of age, 28 of the infants were diagnosed as HIV-infected, and the 98 uninfected infants served as a control group. The infected and uninfected infants did not differ with respect to mean gestational age, birth weight, ethnicity, or rates of maternal separation and death. Results. By 3 months of age, the mean mental and motor scores of the infected infants were significantly lower than those of the uninfected controls. Furthermore, the initial differences between the two groups increased over time, as many of the infected infants became increasingly delayed. Although the infected infants tended to perform more poorly than the uninfected infants, nearly one third of the infected infants exhibited relatively normal cognitive development and half demonstrated relatively normal motor development. Conclusions. Over the first 24 months of life, the mean rate of development of HIV-infected infants is significantly slower than that of noninfected infants born to seropositive mothers. This occurs even when the effects are not confounded with those of prenatal drug exposure.

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Relapse to drug and alcohol use: a matter of sensitization

Acta Neuropsychiatrica ◽

10.1017/s0924270800035766 ◽

2000 ◽

Vol 12 (1) ◽

pp. 5-8 ◽

Cited By ~ 2

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.

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Does Prenatal Methamphetamine Exposure Induce Cross-sensitization to Cocaine and Morphine in Adult Male Rats?

Prague Medical Report ◽

10.14712/23362936.2015.17 ◽

2012 ◽

Vol 113 (3) ◽

pp. 189-205 ◽

Cited By ~ 15

Author(s):

Romana Šlamberová ◽

A. Yamamotová ◽

M. Pometlová ◽

B. Schutová ◽

L. Hrubá ◽

...

Keyword(s):

Adult Male ◽

Analgesic Effect ◽

Drug Exposure ◽

Prenatal Drug Exposure ◽

Male Rats ◽

Daily Injection ◽

Challenge Dose ◽

Drug Seeking ◽

Seeking Behavior ◽

Plantar Test

The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to challenge dose of cocaine or morphine. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male offspring (prenatally MA- or saline-exposed) were divided to groups with challenge doses of saline (1 ml/kg), cocaine (5 mg/kg) or morphine (5 mg/kg). Behavior in unknown environment was examined in Laboras, nociception in Plantar test, and active drug-seeking behavior in conditioned place preference (CPP). Our data demonstrate that cocaine increased the exploratory activity in Laboras test in prenatally saline-exposed, but decreased it in prenatally MA-exposed rats. An analgesic effect of cocaine was demonstrated only by the tail withdrawal and it was independent of the prenatal drug exposure. CPP test showed that prenatal MA exposure induced rather tolerance than sensitization to cocaine. In contrast to cocaine effects, morphine decreased rearing activity in both, prenatally MA-exposed and saline-exposed rats, and locomotion only in prenatally MA-exposed rats in the Laboras. In the Plantar test, the results demonstrated that morphine had an analgesic effect in prenatally saline-exposed rats but this effect was suppressed in prenatally MA-exposed rats. In the CPP test morphine induced drug-seeking behavior, which however was not affected by prenatal drug exposure. Thus, our data demonstrate that there is a cross-effect between prenatal MA exposure and the challenge dose of other drug in adulthood, however drug-seeking behavior is not increased by prenatal MA exposure as we expected.

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Prenatal Drug Exposure and Behavioral Outcomes in Adolescence: The Role of Neighborhood Violence and Social Support

PsycEXTRA Dataset ◽

10.1037/e685302011-001 ◽

2011 ◽

Author(s):

Stacy Howes ◽

Cindy M. Schaeffer ◽

Maureen M. Black

Keyword(s):

Social Support ◽

Drug Exposure ◽

Behavioral Outcomes ◽

Prenatal Drug Exposure ◽

Neighborhood Violence

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Are patients of a large paediatric nephrology department an appropriate population to investigate long-term effects of prenatal drug exposure in a retrospective approach?

Reproductive Toxicology ◽

10.1016/j.reprotox.2020.04.030 ◽

2020 ◽

Vol 97 ◽

pp. 3-4

Author(s):

Stephanie Padberg ◽

Julia Thumfart ◽

Svenja J. Börning ◽

Dominik Müller ◽

Katarina Dathe ◽

...

Keyword(s):

Drug Exposure ◽

Prenatal Drug Exposure ◽

Paediatric Nephrology ◽

Long Term Effects

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The Adenosine A2A Receptor Activation in Nucleus Accumbens Suppress Cue-Induced Reinstatement of Propofol Self-administration in Rats

Neurochemical Research ◽

10.1007/s11064-021-03238-9 ◽

2021 ◽

Author(s):

Zhanglei Dong ◽

Bingwu Huang ◽

Chenchen Jiang ◽

Jiangfan Chen ◽

Han Lin ◽

...

Keyword(s):

Nucleus Accumbens ◽

D2 Receptor ◽

Fixed Ratio ◽

Receptor Activation ◽

Addictive Behaviors ◽

Self Administration ◽

A2a Receptors ◽

Mediated Effects ◽

Seeking Behavior ◽

Adenosine A2a

AbstractPropofol has shown strong addictive properties in rats and humans. Adenosine A2A receptors (A2AR) in the nucleus accumbens (NAc) modulate dopamine signal and addictive behaviors such as cocaine- and amphetamine-induced self-administration. However, whether A2AR can modulate propofol addiction remains unknown. AAV-shA2AR was intra-NAc injected 3 weeks before the propofol self-administration training to test the impacts of NAc A2AR on establishing the self-administration model with fixed ratio 1 (FR1) schedule. Thereafter, the rats were withdrawal from propofol for 14 days and tested cue-induced reinstatement of propofol seeking behavior on day 15. The propofol withdrawal rats received one of the doses of CGS21680 (A2AR agonist, 2.5–10.0 ng/site), MSX-3 (A2AR antagonist, 5.0–20.0 μg/site) or eticlopride (D2 receptor (D2R) antagonist, 0.75–3.0 μg/site) or vehicle via intra-NAc injection before relapse behavior test. The numbers of active and inactive nose-poke response were recorded. Focal knockdown A2AR by shA2AR did not affect the acquisition of propofol self-administration behavior, but enhance cue-induced reinstatement of propofol self-administration compared with the AAV-shCTRLgroup. Pharmacological activation of the A2AR by CGS21680 (≥ 5.0 ng/site) attenuated cue-induced reinstatement of propofol self-administration behavior. Similarly, pharmacological blockade of D2R by eticlopride (0.75–3.0 μg/site) attenuated propofol seeking behavior. These effects were reversed by the administration of MSX-3 (5.0–20.0 μg/site). The A2AR- and D2R-mediated effects on propofol relapse were not confounded by the learning process, and motor activity as the sucrose self-administration and locomotor activity were not affected by all the treatments. This study provides genetic and pharmacological evidence that NAc A2AR activation suppresses cue-induced propofol relapse in rats, possibly by interacting with D2R.

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Pediatric Psychopharmacology and the Interaction between Drugs and the Developing Brain

The Canadian Journal of Psychiatry ◽

10.1177/070674379804300605 ◽

1998 ◽

Vol 43 (6) ◽

pp. 582-584 ◽

Cited By ~ 36

Author(s):

Benedetto Vitiello

Keyword(s):

Drug Exposure ◽

Imaging Techniques ◽

Quantitative Imaging ◽

Adult Life ◽

Prenatal Drug Exposure ◽

Developing Brain ◽

Teratogenic Effects ◽

Pharmacological Agents ◽

Early Inhibition ◽

Interaction Between Drugs

With increasing frequency, psychotropic medications are being prescribed to young children, often for long periods of time. The interaction between psychotropics and the developing brain has not been systematically investigated in humans. Data collected from animals suggest that developing neurotransmitter systems can be exquisitely sensitive to early inhibition or stimulation by pharmacological agents, which can lead to permanent changes in adult life. Most of these data are collected from rodents, and their extrapolation to humans is difficult. More relevant models could be developed, for instance using primates. In humans, the focus of research has traditionally been on the possible teratogenic effects of prenatal drug exposure. Recently introduced quantitative imaging techniques can offer new approaches to studying the effects of psychotropics on the developing brain. This research has clear implications for the safety and efficacy of psychopharmacologic drug use in children.

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