Widespread but regionally specific effects of experimenter‐ versus self‐administered morphine on dendritic spines in the nucleus accumbens, hippocampus, and neocortex of adult rats

Abstract

We studied the effects of self‐administered (SA) vs. experimenter‐administered (EA) morphine on dendritic spines in the hippocampal formation (CA1 and dentate), nucleus accumbens shell (NAcc‐s), sensory cortex (Par1 and Oc1), medial frontal cortex (Cg3), and orbital frontal cortex (AID) of rats. Animals in the SA group self‐administered morphine in 2‐h sessions (0.5 mg/kg/infusion, i.v.) for an average of 22 sessions and animals in the EA group were given daily i.v. injections of doses that approximated the total session dose for matched rats in Group SA (average cumulative dose/session of 7.7 mg/kg). Control rats were given daily i.v. infusions of saline. One month after the last treatment the brains were processed for Golgi‐Cox staining. In most brain regions (Cg3, Oc1, NAcc‐s) morphine decreased the density of dendritic spines, regardless of mode of administration (although to a significantly greater extent in Group SA). However, only SA morphine decreased spine density in the hippocampal formation and only EA morphine decreased spine density in Par1. Interestingly, in the orbital frontal cortex morphine significantly increased spine density in both Groups SA and EA, although to a much greater extent in Group SA. We conclude: 1) Morphine has persistent (at least 1 month) effects on the density of dendritic spines in many brain regions, and on many different types of cells (medium spiny neurons, pyramidal cells, and granule cells); 2) The effect of morphine on spine density (and presumably synaptic organization) varies as a function of both brain region and mode of drug administration; and 3) The ability of morphine to remodel synaptic inputs in a regionally specific manner may account for the many different long‐term sequelae associated with opioid use. Synapse 46:271–279, 2002. © 2002 Wiley‐Liss, Inc.

Homers regulate drug-induced neuroplasticity: Implications for addiction

“…The structural changes induced by the above drugs are detectable at 24-48 hrs following discontinuation of chronic drug treatment [207] and can be observed for up 3.5 months [202,209]. Similar to nicotine and psychomotor stimulants, the structural plasticity associated with morphine treatment has been described a month after the last treatment [210,211]. However, the morphological changes induced by chronic morphine experience are very different from those induced by nicotine and stimulant drugs, characterized by marked decreases in spine density in both the shell of the NAC and medial PFC and decreased dendritic branching [210,211].…”

“…Similar to nicotine and psychomotor stimulants, the structural plasticity associated with morphine treatment has been described a month after the last treatment [210,211]. However, the morphological changes induced by chronic morphine experience are very different from those induced by nicotine and stimulant drugs, characterized by marked decreases in spine density in both the shell of the NAC and medial PFC and decreased dendritic branching [210,211]. More well-characterized for hippocampus, chronic alcohol produces yet another distinct set of morphological changes within dendrites, compared to other drugs of abuse [212][213][214][215], characterized by increases in the ratio of wide and stubby spines to thin and mushroom-shaped spines [212][213][214].…”

EEG spectral power and mean frequencies in early heroin abstinence

“…Speculatively, opioids ability to remodel the density of dendritic spines and thus to affect the synaptic inputs may be assumed as an underlying cause of long-term neuronal oscillation frequency changes in chronic heroin abusers (Morozov and Bogolepov, 1984;Robinson et al, 2002).…”

Extracellular Matrix Plasticity and GABAergic Inhibition of Prefrontal Cortex Pyramidal Cells Facilitates Relapse to Heroin Seeking

“…At the cellular level, changes in neuronal connectivity and neuronal physiology have been observed after opiate exposure. For instance, morphine treatment leads to changes in the complexity of dendritic branching on cells in the neocortex and hippocampus during development (Hammer et al, 1989) and affects the number of synaptic spines and dendritic arborizations of the neurons in the mPFC and NAc (Robinson and Kolb, 1999;Robinson et al, 2002). In addition to structural changes, opiate exposure also results in a change in synapse physiology of neurons in the ventral-tegmental area (Saal et al, 2003), hippocampus (Pu et al, 2002), and NAc (Dong et al, 2007), and leads to long-lasting changes in dopamine and acetylcholine release at nerve terminals in the striatum (Tjon Tien Ril et al, 1993;Tjon et al, 1994;Vanderschuren et al, 2001).…”