Reinforcements from the first drug experience can predict later drug habits and/or addiction: Results with coffee, cigarettes, alcohol, barbiturates, minor and major tranquilizers, stimulants, marijuana, hallucinogens, heroin, opiates and cocaine

Previously we found that outbred male Sprague-Dawley rats can be classified as either low or high cocaine responders (LCRs or HCRs, respectively), based on their open-field locomotor response to acute cocaine (COC; 10 mg/kg, i.p.). Here, we extended this analysis to amphetamine (AMPH; 0.5, 1, and 5 mg/kg, i.p.) and found that the individual differences in behavioral activation were not as pronounced as with COC. This was confirmed with observational analysis of behaviors. Differences in drug-induced activation could involve differential dopamine transporter (DAT) function/trafficking. To address this possibility, we measured [ 3 H]DA uptake into dorsal striatal synaptosomes prepared from rats injected 30 min earlier with saline, COC, or AMPH to determine DAT activity, and radioligand binding to determine the total number of DATs. Striatal [ 3 H]DA uptake in COC-treated HCRs was significantly higher than in LCRs. Furthermore, regardless of LCR/HCR classification, uptake in individual COC-treated rats was significantly correlated with their locomotor behavior in the 30 min after drug administration. In contrast, AMPH-treated rats did not differ in uptake, nor were uptake and locomotor activity correlated. DAT number did not differ between LCRs or HCRs, or between AMPH-treated rats. In addition, when individual differences in COC-induced behavior were no longer detected in LCRs and HCRs 1 week after initial classification, uptake was also similar. Together, these results suggest that a difference in expression of functional DATs on the cell surface contributes to the individual differences observed in COC-induced, but not AMPH-induced, behavioral activation of rats.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Individual Differences in Cocaine- and Amphetamine-Induced Activation of Male Sprague–Dawley Rats: Contribution of the Dopamine Transporter

Briegleb

Gulley

Hoover

et al. 2004

“…It has been demonstrated that use of multiple stimuli as cues in the CPP procedure produces stronger conditioning, as opposed to the procedure based on single modality stimulus (Mucha et al, 1982;Barr et al, 1985). This method of establishing CPP using only one drug pairing corresponds better to the literature on humans indicating that the initial drug experience is an important factor contributing to later drug use (Haertzen et al, 1983). Moreover, it eliminates other possible confounding factors like tolerance to the rewarding effect of morphine (Shippenberg et al, 1988).…”

Section: Effects Of Gcp II Inhibition On Morphine-induced Conditionedmentioning

confidence: 92%

Morphine Tolerance and Reward but not Expression of Morphine Dependence are Inhibited by the Selective Glutamate Carboxypeptidase II (GCP II, NAALADase) Inhibitor, 2-PMPA

Popik

Kozela

Wróbel

et al. 2002

Inhibition of glutamate carboxypeptidase II (GCP II; NAALADase) produces a variety of effects on glutamatergic neurotransmission. The aim of this study was to investigate effects of GCP II inhibition with the selective inhibitor, 2-PMPA, on: (a) development of tolerance to the antinociceptive effects, (b) withdrawal, and (c) conditioned reward produced by morphine in C57/Bl mice. The degree of tolerance was assessed using the tail-flick test before and after 6 days of twice daily (b.i.d.) administration of 2-PMPA and 10 mg/kg of morphine. Opioid withdrawal was measured 3 days after twice daily morphine (30 or 10 mg/kg) administration, followed by naloxone challenge. Conditioned morphine reward was investigated using conditioned place preference with a single morphine dose (10 mg/kg). High doses of 2-PMPA inhibited the development of morphine tolerance (resembling the effect of 7.5 mg/kg of the NMDA receptor antagonist, memantine) while not affecting the severity of withdrawal. A high dose of 2-PMPA (100 mg/kg) also significantly potentiated morphine withdrawal, but inhibited both acquisition and expression of morphine-induced conditioned place preference. Memantine inhibited the intensity of morphine withdrawal as well as acquisition and expression of morphine-induced conditioned place preference. In addition, 2-PMPA did not affect learning or memory retrieval in a simple two-trial test, nor did it produce withdrawal symptoms in morphinedependent, placebo-challenged mice. Results suggest involvement of GCP II (NAALADase) in phenomena related to opioid addiction.

“…Variation in sensitivity to the locomotor stimulant effect of amphetamines and opioids is heritable (Belknap et al, 1998;Phillips et al, 2008;Gill and Boyle, 2008;Oliverio et al, 1975;Philip et al, 2010). Because epidemiological studies indicate that sensitivity to drug liking in humans can predict an individual's susceptibility to drug abuse (Haertzen et al, 1983;Schuckit, 2009), drug sensitivity and abuse are hypothesized to share a genetic basis. This hypothesis is supported by genetic association studies in humans that have identified genes that influence both acute sensitivity (Hamidovic et al, 2009(Hamidovic et al, , 2010Lott et al, 2005Lott et al, , 2006Dlugos et al, 2011) and dependence (Ho et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Csnk1e Is a Genetic Regulator of Sensitivity to Psychostimulants and Opioids

Bryant

Parker

Zhou

et al. 2011

Csnk1e, the gene encoding casein kinase 1-epsilon, has been implicated in sensitivity to amphetamines. Additionally, a polymorphism in CSNK1E was associated with heroin addiction, suggesting that this gene may also affect opioid sensitivity. In this study, we first conducted genome-wide quantitative trait locus (QTL) mapping of methamphetamine (MA)-induced locomotor activity in C57BL/6J (B6) Â DBA/ 2J (D2)-F 2 mice and a more highly recombinant F 8 advanced intercross line. We identified a QTL on chromosome 15 that contained Csnk1e (63-86 Mb; Csnk1e ¼ 79.25 Mb). We replicated this result and further narrowed the locus using B6.D2 Csnk1e and D2.B6 Csnk1e reciprocal congenic lines (78-86.8 and 78.7-81.6 Mb, respectively). This locus also affected sensitivity to the m-opioid receptor agonist fentanyl. Next, we directly tested the hypothesis that Csnk1e is a genetic regulator of sensitivity to psychostimulants and opioids. Mice harboring a null allele of Csnk1e showed an increase in locomotor activity following MA administration. Consistent with this result, coadministration of a selective pharmacological inhibitor of Csnk1e (PF-4800567) increased the locomotor stimulant response to both MA and fentanyl. These results show that a narrow genetic locus that contains Csnk1e is associated with differences in sensitivity to MA and fentanyl. Furthermore, gene knockout and selective pharmacological inhibition of Csnk1e define its role as a negative regulator of sensitivity to psychostimulants and opioids.