Drive and Reinforcement Circuitry in the Brain: Origins, Neurotransmitters, and Projection Fields

Abstract

Brain stimulation has identified two central subsets of stimulation sites with motivational relevance. First, there is a large and disperse set of sites where stimulation is reinforcing, increasing the frequency of the responses it follows, and second, a much more restricted set of sites where-along with reinforcement-stimulation also has drive-like effects, instigating feeding, copulation, predation, and other motivated acts in otherwise sated or peaceful animals. From this work a dispersed but synaptically interconnected network of reinforcement circuitry is emerging: it includes afferents to the ventral tegmental area and substantia nigra; the dopamine systems themselves; glutamatergic afferents to the striatum; and one of two dopamine-receptor-expressing efferent pathways of the striatum. Stimulation of a limited subset of these sites, including descending inhibitory medial forebrain bundle fibers, induces both feeding and reinforcement, and suggests the possibility of a subset of fibers where stimulation has both drive-like and reinforcing effects. This review stresses the common findings of sites and connectivity between electrical and optogenetic studies of core drive and reinforcement sites. By doing so, it suggests the biological importance of optogenetic follow-up of less-publicized electrical stimulation findings. Such studies promise not only information about origins, neurotransmitters, and connectivity of related networks, by covering more sensory and at least one putative motor component they also promote a much deeper understanding of the breadth of motivational function.

Long-term treatment with a glucagon-like peptide-1 receptor agonist reduces ethanol intake in male and female rats

“…As the present findings preliminary pin point areas and neurotransmitters possibly contributing to the ability of dulaglutide to reduce ethanol intake, the downstream mechanisms of dulaglutide should be evaluated in more detail in upcoming studies. Future studies should also elucidate the effects of dulaglutide on other brain areas and neurotransmitters that participate in AUD processes 33 .…”

“…The male (experiment four) and the female (experiment five) rats were injected (sc) once weekly, for a total of 5 weeks, with dulaglutide (0.1 mg/kg) or vehicle (corresponding to ethanol sessions 1-15). The rats were exposed to the intermittent access ethanol paradigm for another six untreated weeks (corresponding to ethanol sessions [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Ethanol, water, food intake and body weight were measured during baseline, active treatment and during treatment discontinuation.…”

How expectations influence pain

“…This idea is supported by imaging data indicating engagement of periaqueductal gray (PAG) during offset analgesia. 55 We have recently reported a 'mirror' increase (ie, onset hyperalgesia) using a stimulus paradigm that is the inverse of that used by Coghill's group to demonstrate offset analgesia (see Alter et al, abstract 2018, IASP Congress proceedings).…”

The Urge to Fight: Persistent Escalation by Alcohol and Role of NMDA Receptors in Mice

“…Glutamate-dependent forms of plasticity are necessary for the long-term behavioral consequences of alcohol to occur ( Brodie, 2002 ; Broadbent et al, 2003 ), perhaps altering the perceived outcome of aggression rewards. Indeed, appetitive responses are particularly sensitive to synaptic changes in posterior VTA DA neurons ( Wise and McDevitt, 2018 ), and it is tempting to hypothesize that biogenic amines and amino acids play a concerted role in the development of alcohol-escalated aggressive motivation. In an apparent dissociation from other forms of behavioral sensitization, the expression of alcohol-escalated motivation to fight is not readily attenuated by iGluR antagonists at dose ranges that are free from disrupting performance measures, as observed herein ( Figure 5 ).…”