Cocaine self‐administration alters the morphology of dendrites and dendritic spines in the nucleus accumbens and neocortex

Abstract

We studied the influence of cocaine use on the structure of neurons in brain regions that contribute to its rewarding effects by allowing rats to self-administer cocaine (0.33 mg/infusion) for 1 h a day for 1 month. Control animals were left undisturbed or allowed to work for food for the same period of time. After an additional 1 month drug-free period the brains were processed for Golgi-Cox staining. In rats that self-administered cocaine, but not rats that worked for food, there was a significant increase in dendritic branching and in the density of dendritic spines on medium spiny neurons in the shell of the nucleus accumbens and on pyramidal cells in the prefrontal and parietal (but not occipital) cortex. There was also a 2.6-fold increase in the incidence of spines with multiple heads (branched spines) on medium spiny neurons. Finally, in the prefrontal cortex some of the apical dendrites of pyramidal cells appeared misshaped, having large bulbous structures on their terminal tips. We speculate that cocaine self-administration experience alters patterns of synaptic connectivity within limbocortical circuitry that is thought to contribute to cocaine's incentive motivational effects and may have neuropathological effects in frontal areas involved in decision making and judgment. Together, these two classes of drug-induced neuroadaptations may contribute to the development of addiction.

Short-term withdrawal from developmental exposure to cocaine activates the glucocorticoid receptor and alters spine dynamics

“…Our data are in contrast with previous works, showing increased cortical spine density after long-term withdrawal (Robinson et al, 2001;Robinson and Kolb, 1999): however, besides the different duration of abstinence, these data were obtained in adult animals whereas our findings are in line with a reduction in cortical spine density observed following cocaine treatment during adolescence (Gourley et al, 2012a).…”

Short-term withdrawal from developmental exposure to cocaine activates the glucocorticoid receptor and alters spine dynamics

“…Our data are in contrast with previous works, showing increased cortical spine density after long-term withdrawal (Robinson et al, 2001;Robinson and Kolb, 1999): however, besides the different duration of abstinence, these data were obtained in adult animals whereas our findings are in line with a reduction in cortical spine density observed following cocaine treatment during adolescence (Gourley et al, 2012a).…”

Experience-dependent effects of cocaine self-administration/conditioning on prefrontal and accumbens dopamine responses.

“…In other words, a cue-induced expectation of nonreward (or no cocaine) appears to have dampened rather than enhanced the dopaminergic response to cocaine. This finding is consistent in theory with other work indicating that cocaine and natural rewards yield unequal impact and outcomes on behavioral and neural systems (Ciccocioppo, Martin-Fardon, & Weiss, 2004; Robinson, Gorny, Mitton, & Kolb, 2001). Though these particular current findings do not correspond with neuronal learning theory, it may be the case that, as indicated above, in vivo microdialysis measurements in the NAcc reflect a distinctly different aspect of cue-induced DA modulation than what is revealed through neural firing responses to reward prediction errors.…”

HIV-1 Vpr Causes Neuronal Apoptosis andIn VivoNeurodegeneration

“…Nevertheless, the present studies indicate that the neurotoxic effects of Vpr extend to different neuronal subpopulations, especially in the basal ganglia in conjunction neurobehavioral abnormalities, primarily defined by aberrant motor activity, whereas neuronal injury was not observed in the cortex and cerebellum (data not shown). In fact, synaptophysin immunoreactivity was higher in the cerebral cortices of Tg animals, in keeping with studies showing higher densities of synaptic boutons in animals chronically treated with neurotoxins such as cocaine (Robinson et al, 2001). Herein, Vpr expression was highest in the cortex and basal ganglia, likely reflecting higher densities of microglia and perivascular macrophages in these regions (Lawson et al, 1990).…”

Short-term withdrawal from developmental exposure to cocaine activates the glucocorticoid receptor and alters spine dynamics

“…Our data are in contrast with previous works, showing increased cortical spine density after long-term withdrawal (Robinson et al, 2001;Robinson and Kolb, 1999): however, besides the different duration of abstinence, these data were obtained in adult animals whereas our findings are in line with a reduction in cortical spine density observed following cocaine treatment during adolescence (Gourley et al, 2012a).…”

Experience-dependent effects of cocaine self-administration/conditioning on prefrontal and accumbens dopamine responses.

“…In other words, a cue-induced expectation of nonreward (or no cocaine) appears to have dampened rather than enhanced the dopaminergic response to cocaine. This finding is consistent in theory with other work indicating that cocaine and natural rewards yield unequal impact and outcomes on behavioral and neural systems (Ciccocioppo, Martin-Fardon, & Weiss, 2004; Robinson, Gorny, Mitton, & Kolb, 2001). Though these particular current findings do not correspond with neuronal learning theory, it may be the case that, as indicated above, in vivo microdialysis measurements in the NAcc reflect a distinctly different aspect of cue-induced DA modulation than what is revealed through neural firing responses to reward prediction errors.…”

HIV-1 Vpr Causes Neuronal Apoptosis andIn VivoNeurodegeneration

“…Nevertheless, the present studies indicate that the neurotoxic effects of Vpr extend to different neuronal subpopulations, especially in the basal ganglia in conjunction neurobehavioral abnormalities, primarily defined by aberrant motor activity, whereas neuronal injury was not observed in the cortex and cerebellum (data not shown). In fact, synaptophysin immunoreactivity was higher in the cerebral cortices of Tg animals, in keeping with studies showing higher densities of synaptic boutons in animals chronically treated with neurotoxins such as cocaine (Robinson et al, 2001). Herein, Vpr expression was highest in the cortex and basal ganglia, likely reflecting higher densities of microglia and perivascular macrophages in these regions (Lawson et al, 1990).…”

Short-term withdrawal from developmental exposure to cocaine activates the glucocorticoid receptor and alters spine dynamics

“…Our data are in contrast with previous works, showing increased cortical spine density after long-term withdrawal (Robinson et al, 2001;Robinson and Kolb, 1999): however, besides the different duration of abstinence, these data were obtained in adult animals whereas our findings are in line with a reduction in cortical spine density observed following cocaine treatment during adolescence (Gourley et al, 2012a).…”

Experience-dependent effects of cocaine self-administration/conditioning on prefrontal and accumbens dopamine responses.

“…In other words, a cue-induced expectation of nonreward (or no cocaine) appears to have dampened rather than enhanced the dopaminergic response to cocaine. This finding is consistent in theory with other work indicating that cocaine and natural rewards yield unequal impact and outcomes on behavioral and neural systems (Ciccocioppo, Martin-Fardon, & Weiss, 2004; Robinson, Gorny, Mitton, & Kolb, 2001). Though these particular current findings do not correspond with neuronal learning theory, it may be the case that, as indicated above, in vivo microdialysis measurements in the NAcc reflect a distinctly different aspect of cue-induced DA modulation than what is revealed through neural firing responses to reward prediction errors.…”

HIV-1 Vpr Causes Neuronal Apoptosis andIn VivoNeurodegeneration

“…Nevertheless, the present studies indicate that the neurotoxic effects of Vpr extend to different neuronal subpopulations, especially in the basal ganglia in conjunction neurobehavioral abnormalities, primarily defined by aberrant motor activity, whereas neuronal injury was not observed in the cortex and cerebellum (data not shown). In fact, synaptophysin immunoreactivity was higher in the cerebral cortices of Tg animals, in keeping with studies showing higher densities of synaptic boutons in animals chronically treated with neurotoxins such as cocaine (Robinson et al, 2001). Herein, Vpr expression was highest in the cortex and basal ganglia, likely reflecting higher densities of microglia and perivascular macrophages in these regions (Lawson et al, 1990).…”