Behavioural and neurochemical effects of repeated administration of cocaine in rats

Roy, Subhadeep; Bhattacharyya, A.K.; Rubaai, A.

doi:10.1016/0028-3908(78)90148-x

Cited by 74 publications

(21 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1C). As expected (Roy et al, 1978), cocaine dramatically increased rearing. Interestingly, the pattern of rearing behavior across weeks differed between males and females.…”

Section: Resultssupporting

confidence: 85%

Sex differences and effects of cocaine on excitatory synapses in the nucleus accumbens

et al. 2011

View full text Add to dashboard Cite

Human and animal studies indicate that drugs of abuse affect males and females differently, but the mechanism(s) underlying sex differences are unknown. The nucleus accumbens (NAc) is central in the neural circuitry of addiction and medium spiny neurons (MSNs) in the NAc show drug-induced changes in morphology and physiology including increased dendritic spine density. We previously showed in drug-naïve rats that MSN dendritic spine density is higher in females than males. In this study, we investigated sex differences in the effects of cocaine on locomotor activity as well as MSN dendritic spine density and excitatory synaptic physiology in rats treated for 5 weeks followed by 17-21 days of abstinence. Females showed a greater locomotor response to cocaine and more robust behavioral sensitization than males. Spine density was also higher in females and, particularly in the core of the NAc, the magnitude of the cocaine-induced increase in spine density was greater in females. Interestingly, in cocaine-treated females but not males, cocaine-induced behavioral activation during treatment was correlated with spine density measured after treatment. Miniature EPSC (mEPSC) frequency in core MSNs also was higher in females, and increased with cocaine in both the core and shell of females more than males. We found no differences in mEPSC amplitude or paired-pulse ratio of evoked EPSCs, suggesting that sex differences and cocaine effects on mEPSC frequency reflect differences in excitatory synapse number per neuron rather than presynaptic release probability. These studies are the first to demonstrate structural and electrophysiological differences between males and females that may drive sex differences in addictive behavior.

show abstract

“…1C). As expected (Roy et al, 1978), cocaine dramatically increased rearing. Interestingly, the pattern of rearing behavior across weeks differed between males and females.…”

Section: Resultssupporting

confidence: 85%

Sex differences and effects of cocaine on excitatory synapses in the nucleus accumbens

et al. 2011

View full text Add to dashboard Cite

show abstract

“…␣-MSH infu- sions into the brains of cocaine-treated rats induced a significant increase in locomotor activity, and this activity was maintained throughout a 1-h test period. Although cocaine alone is known to induce substantial locomotor activity immediately after administration (Post and Rose, 1976;Roy et al, 1978), we tested animals 3 h after drug treatment, when the locomotor-activating effects are no longer exhibited (Post and Rose, 1976). The results of the current investigation are consistent with previous reports and demonstrate that animals receiving repeated cocaine and then receiving an acute saline infusion (i.c.v.)…”

Section: Discussionsupporting

confidence: 88%

Molecular and Behavioral Interactions Between Central Melanocortins and Cocaine

Alvaro

Taylor²,

Duman³

2003

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Behavioral and molecular studies have established a link between drugs of abuse and the central melanocortin system, particularly the melanocortin 4 receptor (MC4-R). The present study expands this line of investigation to characterization of the neurochemical and behavioral interactions between MC4-R and the psychomotor stimulant, cocaine. The results demonstrate that repeated, but not acute, cocaine administration upregulates MC4-R mRNA expression in the striatum and hippocampus, but not cerebral cortex. Pharmacological studies indicate that the up-regulation of MC4-R expression occurs via dopamine D 1 and D 2 receptor-dependent mechanisms. The D 1 /D 2 antagonist haloperidol and the D 2 -selective antagonist eticlopride mimic the effect of cocaine on MC4-R expression. In addition, coadministration of a D 1 -selective antagonist, SCH 23390 [R-(ϩ)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine], completely blocks the up-regulation of MC4 mRNA by cocaine, demonstrating that D 1 receptor activation is necessary for this response. Moreover, the results demonstrate that cocaine treatment increases behavioral responses (grooming and locomotor activity) to infusions of a melanocortin agonist, indicating that up-regulation of MC4-R expression results in functional consequences. These data further support a role for the melanocortin-MC4-R neuropeptide system in the biochemical and behavioral effects of cocaine.Pro-opiomelanocortin (POMC) serves as a precursor for a number of neuropeptides, including the melanocortins, ␣-, ␤-, and ␥-melanocyte-stimulating hormone (MSH), and adrenocorticotrophic hormone, as well as ␤-endorphin. POMC-expressing neurons are located in the pituitary, the arcuate nucleus of the hypothalamus, and the nucleus of the solitary tract; and the latter two structures send projections to a number of different brain regions, including the mesolimbic dopamine system (Jacobowitz and O 'Donohue, 1978;Eskay et al., 1979). The melanocortin neuropeptides are reported to influence a variety of behavioral and neuroendocrine systems via regulation of central nervous system centers, including grooming, thermoregulation, and learning (Alvaro et al., 1997). The actions of melanocortins are mediated via activation of melanocortin receptors, of which there are five subtypes, all of which belong to the G-protein-coupled receptor superfamily. Two of these, melanocortin-3 and -4 (MC3-R and MC4-R) are expressed in significant levels in the brain and are thereby thought to mediate the central actions of melanocortin neuropeptides.Melanocortins are also reported to play a role in the behavioral and neurochemical actions of opiates, psychostimulants, and alcohol. Early studies indicated that melanocortin treatment could antagonize opiate tolerance and dependence, and even induce opiate withdrawal-like effects in naive animals (Szekaly et al., 1979;Contreras and Takemori, 1984). A preliminary study also found that a selective MC4-R antagonist attenuates the signs of morphine withdrawal tha...

show abstract

“…Because sensitization to cocaine can be seen after even a single pretreatment (O'Neill and Sanger, 1999), changes in pharmacokinetics may not be of primary importance when considering whether sensitization develops or not. However, it could play a role in the increasing magnitude of sensitization seen with multiple drug exposures (Kalivas and Duffy, 1990;Roy et al, 1978).…”

Section: Discussionmentioning

confidence: 99%

Cross‐Sensitization Between the Locomotor Stimulant Effects of Ethanol and Those of Morphine and Cocaine in Mice

Lessov

Phillips

2003

Alcoholism Clin & Exp Res

View full text Add to dashboard Cite

show abstract

Behavioural and neurochemical effects of repeated administration of cocaine in rats

Cited by 74 publications

References 19 publications

Sex differences and effects of cocaine on excitatory synapses in the nucleus accumbens

Sex differences and effects of cocaine on excitatory synapses in the nucleus accumbens

Molecular and Behavioral Interactions Between Central Melanocortins and Cocaine

Cross‐Sensitization Between the Locomotor Stimulant Effects of Ethanol and Those of Morphine and Cocaine in Mice

Contact Info

Product

Resources

About