Does prenatal methamphetamine exposure affect the drug-seeking behavior of adult male rats?

Drug abuse of pregnant women is a growing problem. The effect of prenatal drug exposure may have devastating effect on development of the offsprings that may be long-term or even permanent. One of the most common drug abused by pregnant women is methamphetamine (MA), which is also the most frequently abused illicit drug in the Czech Republic. Our previous studies demonstrated that prenatal MA exposure alters behavior, cognition, pain and seizures in adult rats in sex-specific manner. Our most recent studies demonstrate that prenatal MA exposure makes adult rats more sensitive to acute injection of the same or related drugs than their controls. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the Conditioned place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5 mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg of physiological saline) and controls (without maternal injections). The following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher amphetamine-seeking behavior than both controls. MA as well as morphine induced drug-seeking behavior of adult male rats, however this effect did not differ based on the prenatal MA exposure. In contrast, prenatal MA exposure induced rather tolerance to cocaine than sensitization after the conditioning in the CPP. MDMA and THC did not induce significant effects. Even though the present data did not fully confirmed our hypotheses, future studies are planned to test the drug-seeking behavior also in self-administration test.

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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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Effect of Amphetamine on Adult Male and Female Rats Prenatally Exposed to Methamphetamine

Prague Medical Report ◽

10.14712/23362936.2014.5 ◽

2014 ◽

Vol 115 (1-2) ◽

pp. 43-59 ◽

Cited By ~ 5

Author(s):

Romana Šlamberová ◽

Eva Macúchová ◽

Kateryna Nohejlová ◽

Andrea Štofková ◽

Jana Jurčovičová

Keyword(s):

Spatial Memory ◽

Adult Male ◽

Drug Exposure ◽

Prenatal Drug Exposure ◽

Female Rats ◽

Male Rats ◽

Daily Injection ◽

Drug Seeking ◽

Male And Female ◽

Male And Female Rats

The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to adult amphetamine (AMP) treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed) were administered with AMP (5 mg/kg) or saline (1 ml/kg) in adulthood. Behaviour in unknown environment was examined in open field test (Laboras), active drug-seeking behaviour in conditioned place preference test (CPP), spatial memory in the Morris water maze (MWM), and levels of corticosterone (CORT) were analyzed by enzyme immunoassay (EIA). Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled) regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing) only in prenatally MA-exposed animals. AMP induced sensitization only in male rats, but not in females when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM test, AMP worsened the performance only in females, but not in males. On the other hand, males swam faster after chronic AMP treatment regardless of the prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in females in all measurement settings. In males, prenatal MA exposure and chronic adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult AMP treatment affects behaviour of adult rats, their spatial memory and stress response in sex-specific manner. The effect is also influenced by prenatal drug exposure.

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Inhibition of a cortico-thalamic circuit attenuates cue-induced reinstatement of drug-seeking behavior in “relapse prone” male rats

10.1101/2020.03.01.972224 ◽

2020 ◽

Cited By ~ 1

Author(s):

Brittany N. Kuhn ◽

Paolo Campus ◽

Marin S. Klumpner ◽

Stephen E. Chang ◽

Amanda G. Iglesias ◽

...

Keyword(s):

Individual Differences ◽

Male Rats ◽

Incentive Salience ◽

Top Down ◽

Drug Induced ◽

Drug Seeking ◽

Drug Cues ◽

Cortical Input ◽

Incentive Value ◽

Seeking Behavior

AbstractRelapse often occurs when individuals are exposed to stimuli or cues previously associated with the drug-taking experience. The ability of drug cues to trigger relapse is believed to be a consequence of incentive salience attribution, a process by which the incentive value of reward is transferred to the reward-paired cue. Sign-tracker (ST) rats that attribute enhanced incentive value to reward cues are more prone to relapse compared to goal-tracker (GT) rats that primarily attribute predictive value to such cues. The neurobiological mechanisms underlying this individual variation in relapse propensity remains largely unexplored. The paraventricular nucleus of the thalamus (PVT) has been identified as a critical node in the regulation of cue-elicited behaviors in STs and GTs, including cue-induced reinstatement of drug-seeking behavior. Here we used a chemogenetic approach to assess whether “top-down” cortical input from the prelimbic cortex (PrL) to the PVT plays a role in mediating individual differences in relapse propensity. Chemogenetic inhibition of the PrL-PVT pathway selectively decreased cue-induced reinstatement of drug-seeking behavior in STs, without affecting behavior in GTs. In contrast, cocaine-primed drug-seeking behavior was not affected in either phenotype. Furthermore, when rats were characterized based on a different behavioral phenotype – locomotor response to novelty – inhibition of the PrL-PVT pathway had no effect on either cue- or drug-induced reinstatement. These results highlight an important role for the PrL-PVT pathway in vulnerability to relapse that is driven by individual differences in the propensity to attribute incentive salience to discrete reward cues.

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Methamphetamine self-administration in a runway model of drug-seeking behavior in male rats

Pharmacology Biochemistry and Behavior ◽

10.1016/j.pbb.2018.09.003 ◽

2018 ◽

Vol 175 ◽

pp. 27-32

Author(s):

Mona Akhiary ◽

Erin M. Purvis ◽

Adam K. Klein ◽

Aaron Ettenberg

Keyword(s):

Male Rats ◽

Self Administration ◽

Drug Seeking ◽

Seeking Behavior

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Correction to: Inhibition of a cortico-thalamic circuit attenuates cue-induced reinstatement of drug-seeking behavior in “relapse prone” male rats

Psychopharmacology ◽

10.1007/s00213-021-05919-3 ◽

2021 ◽

Author(s):

Brittany N. Kuhn ◽

Paolo Campus ◽

Marin S. Klumpner ◽

Stephen E. Chang ◽

Amanda G. Iglesias ◽

...

Keyword(s):

Male Rats ◽

Drug Seeking ◽

Seeking Behavior

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Reward-predictive cues elicit maladaptive reward seeking in adolescent rats

10.1101/2020.06.17.157644 ◽

2020 ◽

Author(s):

Andrew T. Marshall ◽

Nigel T. Maidment ◽

Sean B. Ostlund

Keyword(s):

Adult Male ◽

Impulse Control ◽

Male Rats ◽

Impulsive Behavior ◽

Reward Seeking ◽

Reward Delivery ◽

Seeking Behavior ◽

Reward Expectancy ◽

Lever Pressing ◽

Adolescent Rats

AbstractImpulsive behavior during adolescence may stem from a developmental imbalance between motivational and impulse control systems, producing greater urges to pursue reward and weakened capacities to inhibit such actions. Here, we developed a Pavlovian-instrumental transfer (PIT) protocol to assay rats’ ability to suppress cue-motivated reward seeking based on changes in reward expectancy. Traditionally, PIT studies focus on how reward-predictive cues motivate instrumental reward-seeking behavior (lever pressing). However, cues signaling imminent reward delivery also elicit countervailing focal-search responses (food-cup approach). We first examined how reward expectancy (cue-reward probability) influences expression of these competing behaviors. Adult male rats increased rates of lever pressing when presented with cues signaling lower probabilities of reward but focused their activity at the food cup on trials with cues that signaled higher probabilities of reward. We then compared adolescent and adult male rats in their responsivity to cues signaling different reward probabilities. In contrast to adults, adolescent rats did not flexibly adjust their pattern of responding based on the expected likelihood of reward delivery but increased their rate of lever pressing for both weak and strong cues. These findings indicate that impulse control over cue-motivated behavior is fundamentally dysregulated during adolescence, providing a model for studying neurobiological mechanisms of adolescent impulsivity.

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