Comparison of Mesocorticolimbic Neuronal Responses During Cocaine and Heroin Self-Administration in Freely Moving Rats

Abstract

To compare neuronal activity within the mesocorticolimbic circuit during the self-administration of cocaine and heroin, multiple-channel single-unit recordings of spike activity within the rat medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) were obtained during the consecutive selfadministration of cocaine and heroin within the same session. The variety of neuronal responses observed before the lever press are termed anticipatory responses, and those observed after the lever press are called post-drug infusion responses. For the total of the 110 mPFC and 111 NAc neurons recorded, 30-50% of neurons, depending on the individual sessions, had no alteration in spike activity in relation to either cocaine or heroin self-administration. Among the neurons exhibiting significant neuronal responses during a self-administration session, only a small portion (16-25%) of neurons responded similarly under both reinforcement conditions; the majority of neurons (75-84%) responded differently to cocaine and heroin self-administration as revealed by variations in both anticipatory and/or post-drug infusion responses. A detailed video analysis of specific movements to obtain the selfadministration of both drugs provided evidence against the possibility that locomotive differences contributed to the observed differences in anticipatory responses. The overall mean activity of neurons recorded in mPFC and NAc measured across the duration of the session segment for either cocaine or heroin self-administration also was different for some neurons under the two reinforcement conditions. This study provides direct evidence that, in mPFC and NAc, heterogeneous neuronal circuits mediate cocaine and heroin self-administration and that distinct, but overlapping, subpopulations of neurons in these areas become active during operant responding for different reinforcers.

Effects of a Dopamine D3 Receptor Ligand, BP 897, on Acquisition and Expression of Food-, Morphine-, and Cocaine-induced Conditioned Place Preference, and Food-seeking Behavior in Rats

“…However, although BP 897 is more D 3 R-selective than most other available compounds, behavioral data must be interpreted with caution, since it exerts partial agonist activity and is endowed with a complex receptor-binding profile. Nevertheless, the present results are in keeping with studies indicating that different neurobiological mechanisms subserve the appetitive value of food and drugs of abuse, and that opiates and cocaine activate neuronal circuits that are in part different (Chang et al, 1998;Miyazaki et al, 1998;Carelli et al, 2000).…”

Blockade by the Cannabinoid CB1 Receptor Antagonist, Rimonabant (SR141716), of the Potentiation by Quinelorane of Food-Primed Reinstatement of Food-Seeking Behavior

“…Although one source of discrepancy between reports may be due, at least in part, to procedural differences (ie between-vs within-session extinction), these results might indicate that different neuronal circuits mediate a similar behavior driven by either drugs of abuse or natural reward. In fact, electrophysiological studies clearly indicated that cocaine, heroine, and food activated different neuronal populations in the NAcc (Chang et al, 1998;Miyazaki et al, 1998;Carelli et al, 2000). In contrast, rimonabant appears to reduce specifically the potentiation by quinelorane of the motivational strength of food pellets.…”

Loss of BDNF Signaling in D1R-Expressing NAc Neurons Enhances Morphine Reward by Reducing GABA Inhibition

“…Although a growing body of evidence demonstrates some shared and some distinct molecular, cellular, and circuit mechanisms between psychostimulant and opiate action (Albertson et al, 2006;Badiani et al, 2011;Chang et al, 1998;Koo et al, 2012;Nestler, 2005), the contribution of D1-type vs D2-type NAc MSNs to morphine reward remains unknown.…”