Psychomotor Stimulant Addiction: A Neural Systems Perspective

257

206

Cannabis use is a hypothesized gateway to subsequent abuse of other drugs such as heroin. We currently assessed whether D-9-tetrahydrocannabinol (THC) exposure during adolescence modulates opiate reinforcement and opioid neural systems in adulthood. Long-Evan male rats received THC (1.5 mg/kg intraperitoneally (i.p.)) or vehicle every third day during postnatal days (PNDs) 28-49. Heroin self-administration behavior (fixed ratio-1; 3-h sessions) was studied from young adulthood (PND 57) into full adults (PND 102). THC-pretreated rats showed an upward shift throughout the heroin self-administration acquisition (30 mg/kg/infusion) phase, whereas control animals maintained the same pattern once stable intake was obtained. Heightened opiate sensitivity in THC animals was also evidenced by higher heroin consumption during the maintenance phase (30 and 60 mg/kg/infusion) and greater responding for moderate-low heroin doses (dose-response curve: 7.5, 15, 30, 60, and 100 mg/kg/injection). Specific disturbance of the endogenous opioid system was also apparent in the brain of adults with adolescent THC exposure. Striatal preproenkephalin mRNA expression was exclusively increased in the nucleus accumbens (NAc) shell; the relative elevation of preproenkephalin mRNA in the THC rats was maintained even after heroin self-administration. Moreover, m opioid receptor (mOR) GTP-coupling was potentiated in mesolimbic and nigrostriatal brainstem regions in THC-pretreated animals. mOR function in the NAc shell was specifically correlated to heroin intake. The current findings support the gateway hypothesis demonstrating that adolescence cannabis exposure has an enduring impact on hedonic processing resulting in enhanced opiate intake, possibly as a consequence of alterations in limbic opioid neuronal populations.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adolescent Cannabis Exposure Alters Opiate Intake and Opioid Limbic Neuronal Populations in Adult Rats

Ellgren

Spano

Hurd

2006

257

206

“…All addictive drugs directly or indirectly influence the dopaminergic projections from the ventral tegmental area (VTA) to the forebrain, and here especially to the amygdala, the ventral pallidum, the prefrontal cortex, and particularly to the nucleus accumbens (NA) (Berke and Hyman, 2000;Wise and Rompre, 1989). The NA plays a crucial role in the reward system of the human brain (Robinson and Berridge, 1993;Koob and Le Moal, 1997;Everitt and Wolf, 2002). Lesions in this brain region abolish the dependence-inducing effects of many drugs of abuse, while stimulation of VTA neurons leads to decreased substance consumption (Di Chiara, 2000).…”

Section: Brain Metabolic Ethanol Effectsmentioning

confidence: 99%

Acute Alcohol Effects on Neuronal and Attentional Processing: Striatal Reward System and Inhibitory Sensory Interactions under Acute Ethanol Challenge

Schreckenberger

Amberg

Scheurich

et al. 2004

The acute influence of ethanol on cerebral activity induces complex psycho-physiological effects that are considerably more pronounced during acute ethanol influx than during maximal blood alcohol concentration (elimination phase). Despite the psychiatric and forensic relevance of these different ethanol effects, the underlying neuronal mechanisms are still unclear. In total, 20 male healthy volunteers were investigated each with three different experimental conditions in a randomized order using an intravenous ethanol challenge (40 g bolus infusion): during influx phase, elimination phase, and under placebo condition. During and after the ethanol (or placebo) infusion, neuropsychological testing of divided attention for visual and auditory stimuli was performed with subsequent 18-FDG PET acquisition. The PET data were analysed using SPM99. Ethanol influx and elimination phase showed focal activations in the bilateral striatum and frontal cortex and deactivations in the occipital cortex. The comparison of influx phase vs elimination phase revealed activations in the anterior cingulate and right prefrontal cortex, relevant deactivations were found in the left superior temporal cortex including Wernicke's area. Neuropsychological testing showed an attentional impairment under ethanol influx compared to ethanol elimination and placebo with an inverse correlation of the attentional performance for auditory stimuli to occipital activity and for visual stimuli to the left temporal (including auditory) cortex. Acute ethanol administration in healthy volunteers stimulates those striatal regions that are considered to have a particular relevance for alcohol craving ('reward system'). Modality specific reciprocal inhibition of sensory cortex activity seems to be relevant for attentional performance during acute alcohol impact.

“…The nucleus accumbens (NAc) and ventral tegmental area (VTA) are two important components of the neural circuitry underlying motivation and reinforcement (Everitt and Wolf, 2002;Kelley et al, 2005), and long-lasting changes in these nuclei are thought to underlie drug addiction (Nestler, 2004). The NAc receives a predominantly dopaminergic projection from the VTA (Swanson, 1982).…”

Section: Introductionmentioning

confidence: 99%

Acute Amphetamine Exposure Selectively Desensitizes κ-Opioid Receptors in the Nucleus Accumbens

Xia

Whistler

et al. 2007

In the present study, we investigated the effects of psychostimulant exposure on k-opioid peptide (KOP) receptor signaling in the rat mesolimbic system. A single subcutaneous (s.c.) injection of amphetamine (2.5 mg/kg) reduced the KOP receptor-mediated inhibition of glutamate release in the nucleus accumbens shell, as a consequence of KOP receptor desensitization. This effect was blocked by dopamine (DA) receptor antagonists or the nonselective opioid antagonist, naltrexone (1 mg/kg, s.c.), and mimicked by the KOP receptor agonists U69593 (0.32 mg/kg, s.c.) and dynorphin (1 mM), indicating that an amphetamine-induced release of dynorphin is producing a long-lasting desensitization of the KOP receptor. Despite the fact that amphetamine also increases dynorphin release in the ventral tegmental area (VTA), KOP receptor function in this region was not affected by amphetamine; there was no difference in the KOP receptor-mediated change in firing rate or resting membrane potential measured in VTA neurons from saline-or amphetaminetreated animals. This study demonstrates that amphetamine can produce regionally selective adaptations in KOP receptor signaling, which may, in turn, alter the effects of subsequent drug exposure.