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

Abstract

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.

Fluoxetine (Prozac) and Serotonin Act on Excitatory Synaptic Transmission to Suppress Single Layer 2/3 Pyramidal Neuron-Triggered Cell Assemblies in the Human Prefrontal Cortex

“…However, in severe or chronic stress, prefrontal control over the dorsal raphe is overcome by increased extracellular level of prefrontal 5-HT (Bland et al, 2003), resulting in disruption of cognitive processes (Cerqueira et al, 2007). Temporary increase in anxiety and threat processing was observed in some patients early in acute SSRI treatment before anxiolytic actions were seen (Kent et al, 1998;Burghardt et al, 2004;Harmer, 2008).…”

Chronic Morphine Selectively Impairs Cued Fear Extinction in Rats: Implications for Anxiety Disorders Associated with Opiate Use

“…For instance, acute opiate or opiate withdrawal affects levels of neurotransmitters such as dopamine, serotonin, and noradrenaline in the mPFC (Bassareo et al, 1995;Bland et al, 2003;Devoto et al, 2002). Repeated opiate use decreases dendritic spine density on pyramidal cells in the mPFC (Robinson and Kolb, 1999), a form of reorganization of structural plasticity that is possibly mediated by molecules regulating neuronal and synaptic structure (Lamprecht and LeDoux, 2004).…”

Differential effects of environmental enrichment and isolation housing on the hormonal and neurochemical responses to stress in the prefrontal cortex of the adult rat: relationship to working and emotional memories

“…It is therefore possible that changes in the amygdala produced by EC could lead to a lower reactivity of this system in response to the presence of a stressor. This lower reactivity of the dopaminergic system in EC rats could be related to a better coping strategy displayed by these animals in response to a stress situation (Carlson et al 1993;Horger and Roth 1996;Berridge et al 1999;Bland et al 2003).…”

“…Interestingly, animals able to control a stress situation show reduced increases of dopamine and serotonin in the PFC (Carlson et al 1993;Berridge et al 1999;Bland et al 2003) and these effects are thought to depend on the ventromedial PFC activation (Amat et al 2005;Maier et al 2006). …”