Neuronal Systems Underlying Behaviors Related to Nicotine Addiction: Neural Circuits and Molecular Genetics

Picciotto, Marina; Corrigall, William A.

doi:10.1523/jneurosci.22-09-03338.2002

Cited by 237 publications

(176 citation statements)

References 39 publications

(43 reference statements)

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“…First, we used a drug self-administration procedure under fixed-ratio and PR schedules that has been employed to assess the reinforcing effects of nicotine and other drugs (Richardson and Roberts, 1996;Picciotto and Corrigall, 2002;Wise, 2004). We then used a reinstatement procedure to assess relapse to drug seeking induced by acute re-exposure to the self-administered drug or other stimuli following extinction of nicotine-maintained responding (Stewart, 2000;Le and Shaham, 2002;Shaham et al, 2003;Weiss, 2005).…”

Section: Discussionmentioning

confidence: 99%

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

Shram

Funk

et al. 2007

Neuropsychopharmacol

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Initiation of smoking behavior typically occurs during adolescence and rarely occurs during adulthood. Despite this epidemiological evidence, relatively little is known about possible neurobiological differences in the response to nicotine in adolescents that might make them more vulnerable to nicotine addiction. In the current study, we assessed nicotine self-administration under fixed ratio (FR) and progressive ratio (PR) reinforcement schedules in adolescent (postnatal day (P) 33-35) and adult (P91-94) rats. We then assessed extinction and reinstatement of nicotine seeking in adulthood in rats that initiated nicotine self-administration during either adolescence or adulthood. Nicotine self-administration (0.03 mg/kg/infusion, i.v.) was higher in adult rats than in adolescent rats under FR5 and PR reinforcement schedules; no age differences in nicotine self-administration were observed under FR1 or FR2 reinforcement schedules. In contrast, saccharin self-administration under FR5 and PR reinforcement schedules was similar in both age groups, potentially ruling out age differences in general performance. Rats that initiated nicotine self-administration as adults demonstrated a greater resistance to extinction of nicotine taking behavior when saline was substituted for nicotine than rats that initiated self-administration as adolescents. Reinstatement of nicotine seeking following nicotine priming injections (0.075, 0.15, 0.3 mg/kg, s.c.) was independent of the age of onset of nicotine self-administration. The present data from established rat models of drug self-administration and drug relapse suggest that nicotine is less reinforcing in adolescent compared with adult rats and that processes other than the reinforcing effects of nicotine may be involved in the greater susceptibility to smoking during the adolescent developmental stage.

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Section: Discussionmentioning

confidence: 99%

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

Shram

Funk

et al. 2007

Neuropsychopharmacol

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“…Nicotine stimulates glutamate release, increasing dopaminergic neurotransmission (Mansvelder and McGehee, 2000). Since the primary excitatory inputs to VTA originate in the PFC (Picciotto and Corrigall, 2002), enhanced excitatory input based on PFCdependent mechanisms also may be a factor. We found that PFC NR2A and NR2B subunit levels were upregulated by approximately 67 and 83%, respectively, after nicotine SA.…”

Section: Discussionmentioning

confidence: 99%

“…However, other neurotransmitter pathways, such as glutamatergic neurons projecting from PFC to VTA, also are involved in the motivational effects of nicotine (Watkins et al, 2000;Picciotto and Corrigall, 2002).…”

Section: Introductionmentioning

confidence: 99%

Upregulation of Ionotropic Glutamate Receptor Subunits within Specific Mesocorticolimbic Regions during Chronic Nicotine Self-Administration

Wang

Chen

Steketee

et al. 2006

Neuropsychopharmacol

119

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Nicotine, an addictive substance, is the major psychoactive component in cigarette smoke. Both a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate (NMDA) receptors are essential for the acute stimulative effects of nicotine on the mesocorticolimbic dopamine system, yet little is known about the effects of chronic nicotine treatment on glutamate receptors. Therefore, we used a model of chronic nicotine self-administration (SA), which emulates important aspects of nicotine intake by humans, to determine whether glutamate receptor subunits were affected. After 18 days of saline vs nicotine SA, ionotropic glutamate receptor subunit levels were determined in brain regions within the mesocorticolimbic system by Western blotting. In prefrontal cortex (PFC), the levels of NMDA receptor subunit 2A (NR2A) and NR2B were increased by 67% (p ¼ 0.04) and 83% (p ¼ 0.027), respectively. In the ventral tegmental area (VTA), glutamate receptor subunit 2/3 (GluR2/3) increased by 34% (p ¼ 0.011). Nicotine SA did not affect the expression of these subunits in dorsal striatum and nucleus accumbens. These findings suggest that chronic nicotine SA selectively increased the levels of ionotropic glutamate receptor subunits in a brain region-specific manner.

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“…Lesioning of mesolimbic VTA neurons projecting to the NAc leads to decreased nicotine self-administration Lanca et al, 2000). Additionally, the effects of nicotine on the dopaminergic system appear to be modulated by glutamatergic and GABAergic neurons (Picciotto and Corrigall, 2002), with nicotine stimulation of gluatamatergic tracts from the prefrontal cortex to the VTA leading to increased DA neuron firing (Kenny and Markou, 2001) and GABA agonism leading to a dampening of DA neuron responses (Cousins et al, 2002). Recent work indicates that nicotine administration causes prolonged depression of GABAergic firing leading to relatively greater excitatory (glutamatergic) input into the mesolimbic DA system and increased DA neuron firing (Mansvelder et al, 2002).…”

Section: Brain Dopamine Responses To Nicotine and Smokingmentioning

confidence: 99%

Functional brain imaging of tobacco use and dependence

Brody

2006

Journal of Psychiatric Research

172

136

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While most cigarette smokers endorse a desire to quit smoking, only about 14% to 49% will achieve abstinence after 6 months or more of treatment. A greater understanding of the effects of smoking on brain function may (in conjunction with other lines of research) result in improved pharmacological (and behavioral) interventions. Many research groups have examined the effects of acute and chronic nicotine/cigarette exposure on brain activity using functional imaging; the purpose of this paper is to synthesize findings from such studies and present a coherent model of brain function in smokers. Responses to acute administration of nicotine/smoking include: a reduction in global brain activity; activation of the prefrontal cortex, thalamus, and visual system; activation of the thalamus and visual cortex during visual cognitive tasks; and increased dopamine (DA) concentration in the ventral striatum/nucleus accumbens. Responses to chronic nicotine/cigarette exposure include decreased monoamine oxidase (MAO) A and B activity in the basal ganglia and a reduction in α 4 β 2 nicotinic acetylcholine receptor (nAChR) availability in the thalamus and putamen. Taken together, these findings indicate that smoking enhances neurotransmission through cortico-basal ganglia-thalamic circuits either by direct stimulation of nAChRs, indirect stimulation via DA release or MAO inhibition, or a combination of these factors. Activation of this circuitry may be responsible for the effects of smoking seen in tobacco dependent subjects, such as improvements in attentional performance, mood, anxiety, and irritability.

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Neuronal Systems Underlying Behaviors Related to Nicotine Addiction: Neural Circuits and Molecular Genetics

Cited by 237 publications

References 39 publications

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

Upregulation of Ionotropic Glutamate Receptor Subunits within Specific Mesocorticolimbic Regions during Chronic Nicotine Self-Administration

Functional brain imaging of tobacco use and dependence

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