Single neuronal responses in medial prefrontal cortex during cocaine self-administration in freely moving rats

Abstract

Chronic single neuronal recording techniques were applied to investigate the involvement of the medial prefrontal cortex (mPFC) during cocaine self-administration in the rat. Rats were trained to press a lever for cocaine under continuous reinforcement and fixed ratio schedules. Different patterns of phasic neuronal activity changes were found to be associated with lever-pressing for cocaine. The neuronal responses could be classified into five categories: 1) increases in neuronal firing before the lever press (15 out of 121 neurons, 12.4%); 2) decreases in neuronal firing before the lever press (13 neurons, 10.7%); 3) increases in neuronal firing after cocaine infusion (4 neurons, 3.3%); 4) decreases in neuronal firing after cocaine infusion (32 neurons, 26.4%); and 5) no alteration of neuronal activity throughout the self-administration session (67 neurons, 55.4%). The anticipatory responses, i.e., neuronal activity appearing before the lever press, were observed for both the continuous reinforcement and fixed ratio schedules. In a few cases, alteration of firing rate was not observed for the first lever press but appeared before subsequent lever presses in fixed ratio schedules. Eliminating cocaine abolished the inhibitory neuronal responses observed after lever press, suggesting that these inhibitory responses after cocaine self-administration were attributable to the pharmacologic effect of cocaine. The data provide initial electrophysiological evidence that the mPFC may play a role in mediating the task sequencing which leads to cocaine self-administration.

Orbitofrontal and Anterior Cingulate Cortex Neurons Selectively Process Cocaine-Associated Environmental Cues in the Rhesus Monkey

“…However, despite the contributions of primate electrophysiolgical studies to basic reward mechanisms, preclinical electrophysiological studies of neuronal activity responses to drugs of abuse and associated cues have, with one exception (Bowman et al, 1996), been conducted in the rodent. Within the rodent literature, there is relatively little work on electrophysiological measures of cortical neuronal activity responses to drug-associated cues (Chang et al, 1997, 1998, 2000; Sun and Rebec, 2006). Given that clinical imaging methods assess measures dependent on blood flow and metabolism which are influenced more by local synaptic processing than action potential generation (Goense and Logothetis, 2008), the current results complement imaging-based measures by assessing the actual neuronal firing that results from that processing.…”

Lateral hypothalamic orexin/hypocretin neurons: A role in reward-seeking and addiction

“…Human functional imaging studies have revealed decreased metabolic activity in mPFC during drug withdrawal (Goldstein and Volkow, 2002) and increased activity in mPFC following exposure to drug cues (Childress et al, 1999; Grant et al, 1996; Maas et al, 1998). In the rat, single neurons in mPFC (in areas shown to project to VTA) are activated during both cocaine and heroin self-administration (Chang et al, 1997a; Chang et al, 1997b; Chang et al, 1998). Therefore, mPFC afferents to VTA are a potential source of VTA glutamate that is involved in reinstatement, learning and expression of drug-seeking behavior.…”

Mesolimbic Neuronal Activity across Behavioral States

“…Neurons in the nucleus accumbens and medial prefrontal cortex (shown here for medial prefrontal cortex) revealed onset or termination of activity correlated with the transitions in the behavioral sequence. (Chang et al 4 With permission from Synapse (NY) .)…”

“…Similar types of pre‐ and post‐lever press or nose‐poke neuronal activity appear during operant responding for all types of rewards so far studied by various investigators. 3,4,27,28,33,38 Variations in neural activity exist if the animal is required to move to obtain a fluid reward or if the reward is a short transient, such as with a fluid reward, including the taste of water, sucrose, or ethanol, instead of a prolonged drug effect.…”

“…The concept of “reward” provides an example of this difficulty. At the outset of our studies, 1‐4 we postulated that such a construct might be readily observable in terms of well‐defined detectable activity patterns. A substantial theoretical background had been suggested 5 that reward evoked by drugs or behavioral circumstance should release dopamine in the nucleus accumbens and cause an excitatory or inhibitory influence on neuronal activity.…”