Behavioral characterization of intracranial self-stimulation from mesolimbic, mesocortical, nigrostriatal, hypothalamic and extra-hypothalamic sites in the non-inbred CD-1 mouse strain

Zacharko, Robert M.; Kasian, Marilyn; Irwin, Jill; Zalcman, Steve; LaLonde, Gerald; MacNeil, Glenda; Anisman, Hymie

doi:10.1016/0166-4328(90)90062-j

Cited by 20 publications

(2 citation statements)

References 75 publications

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“…The ICSS paradigm is based on the operant response of the animals to brain stimulation and can be viewed as the animals' willingness to work to obtain a certain level of stimulation. Although animals will learn operant responses that elicit stimulation in a large number of different brain areas (Zacharko et al, 1990), the medial forebrain bundle was selected in the current study because of the relative lack of motor artifacts upon stimulation in this region, as well as for comparability to earlier studies from our laboratory using other benzodiazepines (Straub et al, 2010;Reynolds et al, 2012). Responding to lower stimulation frequencies after the administration of a drug than those that maintained responding previously is interpreted as 'reward enhancement', and is commonly observed after the administration of drugs of abuse (Wise, 1996).…”

Section: Discussionmentioning

confidence: 99%

Neural Basis of Benzodiazepine Reward: Requirement for α2 Containing GABAA Receptors in the Nucleus Accumbens

Engin

Bakhurin

Smith

et al. 2014

Neuropsychopharmacol

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Despite long-standing concerns regarding the abuse liability of benzodiazepines, the mechanisms underlying properties of benzodiazepines that may be relevant to abuse are still poorly understood. Earlier studies showed that compounds selective for a1-containing GABA A receptors (a1GABA A Rs) are abused by humans and self-administered by animals, and that these receptors may underlie a preference for benzodiazepines as well as neuroplastic changes observed in the ventral tegmental area following benzodiazepine administration. There is some evidence, however, that even L-838, 417, a compound with antagonistic properties at a1GABA A Rs and agonistic properties at the other three benzodiazepine-sensitive GABA A receptor subtypes, is self-administered, and that the a2GABA A Rs may have a role in benzodiazepine-induced reward enhancement. Using a two-bottle choice drinking paradigm to evaluate midazolam preference and an intracranial self-stimulation (ICSS) paradigm to evaluate the impact of midazolam on reward enhancement, we demonstrated that mice carrying a histidine-to-arginine point mutation in the a2 subunit which renders it insensitive to benzodiazepines (a2(H101R) mice) did not prefer midazolam and did not show midazolam-induced reward enhancement in ICSS, in contrast to wild-type controls, suggesting that a2GABA A Rs are necessary for the reward enhancing effects and preference for oral benzodiazepines. Through a viral-mediated knockdown of a2GABA A Rs in the nucleus accumbens (NAc), we demonstrated that a2 in the NAc is necessary for the preference for midazolam. Findings imply that a2GABA A Rs in the NAc are involved in at least some rewardrelated properties of benzodiazepines, which might partially underlie repeated drug-taking behavior.

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Section: Discussionmentioning

confidence: 99%

Neural Basis of Benzodiazepine Reward: Requirement for α2 Containing GABAA Receptors in the Nucleus Accumbens

Engin

Bakhurin

Smith

et al. 2014

Neuropsychopharmacol

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“…The MPFC and CPu also exhibit comparable behavioral and electrophysiological characteristics when stimulated. For example, they are similar with respect to the rate of self-stimulation acquisition (Corbett, Laferrière, & Milner, 1982; Corbett, Silva, & Stellar, 1985), level of arousal associated with the stimulation (arrest reactions; Schenk & Shizgal, 1982; Trzcińska & Bielajew, 1992; Yadin, Guarini, & Gallistel, 1983; Zacharko et al, 1990), currents used to elicit self-stimulation (Nassif, Cardo, Libersat, & Velley, 1985; Schenk, Prince, & Shizgal, 1985), their [ 14 C ]-2-deoxyglucose autoradiography patterns (Yadin et al, 1983), and the degree of epileptogenic activity (Corbett, 1990). In addition, there is some evidence that lesions of either the MPFC or CPu produce qualitatively similar deficits (Brutkowski, 1965; Kolb, 1984), which indicates that the striatum may constitute a component of neural circuitry, with the prefrontal cortex and the mediodorsal thalamic nucleus (Kolb & Tees, 1990).…”

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Functional connections between medial prefrontal cortex and caudate-putamen in brain-stimulation reward of rats.

Trzcińska¹,

Bielajew²

1998

Behavioral Neuroscience

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Rats were trained to self-stimulate for trains of cathodal pulses delivered via electrodes placed in the medial prefrontal cortex (MPFC) and caudate-putamen (CPu). When the pulses were delivered via 9 ipsilateral MPFC and CPu sites alternately, summation varied from 13% to 40%. However, the overall summation for 2 contralateral MPFC-CPu pairs was 5%, thus indicating a greater integration of ipsilateral than contralateral reward signals. When the interval between alternate pulses decreased in 4 of the 9 ipsilateral pairs, the summation also decreased, an outcome consistent with collision of action potentials passing between the MPFC and CPu sites. The size of the collision effect ranged from 15% to 33%. Estimates of conduction velocity varied between 0.4 to 5.4 m/s, with a 1.7 m/s average. According to these values, the neurons connecting the MPFC and CPu self-stimulation sites appear to be slower than the ones that have been shown to link reward fibers that course between posterior brain regions.

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Neural Substrates of Psychostimulant Withdrawal-Induced Anhedonia

D’Souza

Markou

2009

Behavioral Neuroscience of Drug Addiction

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Psychostimulant drugs have powerful reinforcing and hedonic properties and are frequently abused. Cessation of psychostimulant administration results in a withdrawal syndrome characterized by anhedonia (i.e., an inability to experience pleasure). In humans, psychostimulant withdrawal-induced anhedonia can be debilitating and has been hypothesized to play an important role in relapse to drug use. Hence, understanding the neural substrates involved in psychostimulant withdrawal-induced anhedonia is essential. In this review, we first summarize the theoretical perspectives of psychostimulant withdrawal-induced anhedonia. Experimental procedures and measures used to assess anhedonia in experimental animals are also discussed. The review then focuses on neural substrates hypothesized to play an important role in anhedonia experienced after termination of psychostimulant administration, such as with cocaine, amphetamine-like drugs, and nicotine. Both neural substrates that have been extensively investigated and some that need further evaluation with respect to psychostimulant withdrawal-induced anhedonia are reviewed. In the context of reviewing the various neurosubstrates of psychostimulant withdrawal, we also discuss pharmacological medications that have been used to treat psychostimulant withdrawal in humans. This literature review indicates that great progress has been made in understanding the neural substrates of anhedonia associated with psychostimulant withdrawal. These advances in our understanding of the neurobiology of anhedonia may also shed light on the neurobiology of nondrug-induced anhedonia, such as that seen as a core symptom of depression and a negative symptom of schizophrenia.

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Behavioral characterization of intracranial self-stimulation from mesolimbic, mesocortical, nigrostriatal, hypothalamic and extra-hypothalamic sites in the non-inbred CD-1 mouse strain

Cited by 20 publications

References 75 publications

Neural Basis of Benzodiazepine Reward: Requirement for α2 Containing GABAA Receptors in the Nucleus Accumbens

Neural Basis of Benzodiazepine Reward: Requirement for α2 Containing GABAA Receptors in the Nucleus Accumbens

Functional connections between medial prefrontal cortex and caudate-putamen in brain-stimulation reward of rats.

Neural Substrates of Psychostimulant Withdrawal-Induced Anhedonia

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