Non-psychostimulant drugs of abuse and anxiogenic drugs activate with differential selectivity dopamine transmission in the nucleus accumbens and in the medial prefrontal cortex of the rat

Bassareo, Valentina; Petromilli, Paola; Giua, Corrado; Chiara, G. Di

doi:10.1007/bf02246138

Cited by 19 publications

(30 citation statements)

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“…Although it is known that morphine increases DA efflux in the NAc Rada et al, 1991), it has previously been demonstrated that morphine has no effect on DA efflux in the mPFC (Bassareo et al, 1996;Devoto et al, 2002). However, one group has shown that acute morphine at a dose similar to that used in the present study increased the DOPAC/DA ratio in the mPFC in an ex vivo preparation (Vezina et al, 1992).…”

Section: Discussionmentioning

confidence: 49%

Stressor Controllability Modulates Stress-Induced Dopamine and Serotonin Efflux and Morphine-Induced Serotonin Efflux in the Medial Prefrontal Cortex

Bland

Hargrave

Pepin

et al. 2003

Neuropsychopharmacol

137

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It has previously been shown that inescapable (IS) but not escapable (ES) stress potentiates the rewarding properties of morphine as measured by conditioned place preference and psychomotor activation, and that this potentiation may be mediated by dorsal raphe nucleus (DRN) serotonin (5-HT) neurons. The medial prefrontal cortex (mPFC) has been implicated in both reward and stress, and is a projection region of the DRN. The mPFC also contains dopaminergic afferents from the ventral tegmental area, which has been the focus of many studies exploring both the rewarding properties of drugs and the aversive properties of stress. The role of the mPFC in stress/ drug reactivity interactions is largely unknown. The present study usedin vivo microdialysis to examine 5-HT and dopamine (DA) efflux in the mPFC of rats during IS, ES or no stress (NS). IS and ES rats received the stressor in yoked pairs. The stressor consisted of tailshocks that could be terminated for both rats by the ES rats. Large increases in 5-HT and DA levels were observed during IS but not ES or NS. DA and 5-HT efflux were also measured 24 h later in the same rats in response to morphine (3 mg/kg) or saline. Sustained increases in 5-HT levels were observed after morphine in rats that had previously received IS but not in rats that had received ES or NS. No changes in DA efflux were observed after morphine. Thus, 5-HT and DA in the mPFC may be involved in stressor controllability effects, and the sensitization of 5-HT neurons by IS extends to the mPFC and to morphine as a challenge.

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Section: Discussionmentioning

confidence: 49%

Stressor Controllability Modulates Stress-Induced Dopamine and Serotonin Efflux and Morphine-Induced Serotonin Efflux in the Medial Prefrontal Cortex

Bland

Hargrave

Pepin

et al. 2003

Neuropsychopharmacol

137

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“…Unlike appetitive conditioning by drug reinforcement, the aversive response of LiCl conditioning is independent of mesolimbic DA release (Bassareo et al, 1996); therefore, CPA experiments directly test the influence of amphetamines-induced neurotoxicity on associative learning. However, results revealed that LiCl-induced CPA was not affected by METH neurotoxicity, suggesting that dopaminergic deficiency alone does not alter aversive conditioning (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Amphetamines-Induced Neurotoxicity on Appetitive and Aversive Pavlovian Conditioning in Mice

Achat-Mendes

Ali

Itzhak

2005

Neuropsychopharmacol

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The abuse of substituted amphetamines such as methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA/ Ecstasy) can result in neurotoxicity, manifested as the depletion of dopamine (DA) and 5-hydroxytriptamine (5-HT; serotonin) axon terminal markers in humans and animal models. Human METH and MDMA users exhibit impairments in memory and executive functions, which may be a direct consequence of the neurotoxic potential of amphetamines. The objective of this study was to investigate the influence of amphetamines-induced neurotoxicity on Pavlovian learning. Using mouse models of selective DA neurotoxicity (METH; 5 mg/kg Â 3), selective 5-HT neurotoxicity (fenfluramine /FEN; 25 mg/kg Â 4) and dual DA and 5-HT neurotoxicity (MDMA; 15 mg/ kg Â 4), appetitive and aversive conditioning were investigated. Dopaminergic neurotoxicity significantly impaired METH and cocaine conditioned place preference (CPP), but had no effect on LiCl-induced conditioned place aversion (CPA). In contrast, serotonergic neurotoxicity significantly enhanced CPP, and had no effect on CPA. Dual dopaminergic/serotonergic neurotoxicity had no apparent effect on CPP; however, CPA was significantly attenuated. Postmortem analysis revealed that significantly diminished levels of DA and 5-HT markers persisted in the striatum, frontal cortex, hippocampus, and amygdala. These findings suggest that amphetamines-induced dopaminergic and serotonergic neurotoxicity exert opposing influences on the affective state produced by subsequent drug reward, while dual dopaminergic/serotonergic neurotoxicity impairs associative learning of aversive conditioning. Furthermore, results revealed that amphetamines-induced DA and 5-HT neurotoxicity modulates appetitive Pavlovian conditioning similar to other DA and 5-HT neurotoxins. Modulation of Pavlovian conditioning by amphetamines-induced neurotoxicity may be relevant to compulsive drug-seeking behavior in METH and MDMA abusers.

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“…Neuroanatomical studies indicate that dopamine neurons from more rostral portions of the VTA innervate primarily, but not exclusively, the NAc shell, whereas dopamine neurons from C-VTA project predominantly, but not exclusively, to cortical areas (Emson and Koob, 1978;Brog et al, 1993). Moreover, these projections show differential regulation by morphine: morphine increases extracellular dopamine levels in the NAc shell but has no effect in prefrontal cortical areas (Bassareo et al, 1996), whereas morphine withdrawal is associated with decreased extracellular dopamine levels in the NAc shell but increased levels in prefrontal cortex (Acquas et al, 1991;Pothos et al, 1991;Bassareo et al, 1995). Thus, within this framework, it is conceivable that increased PLC␥1 activity in R-VTA dopamine neurons enhances reward to morphine and sucrose while resulting in opposite effects when PLC␥1 activity is enhanced in C-VTA dopamine neurons.…”

Section: Discussionmentioning

confidence: 99%

Phospholipase Cγ in Distinct Regions of the Ventral Tegmental Area Differentially Modulates Mood-Related Behaviors

et al. 2003

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Neurotrophic factor signaling pathways modulate cellular and behavioral responses to drugs of abuse. In addition, chronic exposure to morphine increases expression of phospholipase C␥1 (PLC␥1) (a protein involved in neurotrophic signaling) in the ventral tegmental area (VTA), a neural substrate for many drugs of abuse. Using viral-mediated gene transfer to locally alter the activity of PLC␥1, we show that overexpression of PLC␥1 in rostral portions of the VTA (R-VTA) results in increased morphine place preference, whereas PLC␥1 overexpression in the caudal VTA (C-VTA) results in avoidance of morphine-paired compartments. In addition, overexpression of PLC␥1 in R-VTA causes increased preference for sucrose and increased anxiety-like behavior but does not affect responses to stress or nociceptive stimuli. In contrast, overexpression of PLC␥1 in C-VTA decreases preference for sucrose and increases sensitivity to stress and nociceptive stimuli, although there was a tendency for increased anxiety-like behavior as seen for the R-VTA. These results show that levels of PLC␥1 in the VTA regulate responsiveness to drugs of abuse, natural rewards, and aversive stimuli and point to the possibility that distinct topographical regions within the VTA mediate generally positive versus negative responses to emotional stimuli. Moreover, these data also support a role for drug-induced elevations in PLC␥1 expression in the VTA in mediating long-term adaptations to drugs of abuse and aversive stimuli.

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Non-psychostimulant drugs of abuse and anxiogenic drugs activate with differential selectivity dopamine transmission in the nucleus accumbens and in the medial prefrontal cortex of the rat

Cited by 19 publications

References 0 publications

Stressor Controllability Modulates Stress-Induced Dopamine and Serotonin Efflux and Morphine-Induced Serotonin Efflux in the Medial Prefrontal Cortex

Stressor Controllability Modulates Stress-Induced Dopamine and Serotonin Efflux and Morphine-Induced Serotonin Efflux in the Medial Prefrontal Cortex

Differential Effects of Amphetamines-Induced Neurotoxicity on Appetitive and Aversive Pavlovian Conditioning in Mice

Phospholipase Cγ in Distinct Regions of the Ventral Tegmental Area Differentially Modulates Mood-Related Behaviors

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