Search bioRxiv⌕ Search

Biology subjects

Carrica, L. K.

Publications and source records attributed to Carrica, L. K..

3 recordsLinked to original sources

Timing of methamphetamine exposure during adolescence differentially influences parvalbumin and perineuronal net immunoreactivity in the medial prefrontal cortex of female, but not male, rats

Adolescence involves significant reorganization within the medial prefrontal cortex (mPFC), including modifications to inhibitory neurotransmission mediated through parvalbumin (PV) interneurons and their surrounding perineuronal nets (PNNs). These developmental changes, which result in increased PV neuron activity in adulthood, may be disrupted by drug use resulting in lasting changes in mPFC function and behavior. Methamphetamine (METH), which is a readily available drug used by some adolescents, increases PV neuron activity and could influence the activity-dependent maturational process of these neurons. In the present study, we used male and female Sprague Dawley rats to test the hypothesis that METH exposure influences PV and PNN expression in a sex- and age-specific manner. Rats were injected daily with saline or 3.0 mg/kg METH from early adolescence (EA; 30-38 days old), late adolescence (LA; 40-48 days old), or young adulthood (60-68 days old). One day following exposure, effects of METH on PV cell and PNN expression were assessed using immunofluorescent labeling within the mPFC. METH exposure did not alter male PV neurons or PNNs. Females exposed in early adolescence or adulthood had more PV expressing neurons while those exposed in later adolescence had fewer, suggesting distinct windows of vulnerability to changes induced by METH exposure. In addition, females exposed to METH had more PNNs and more intense PV neuron staining, further suggesting that METH exposure in adolescence uniquely influences development of inhibitory circuits in the female mPFC. This study indicates that the timing of METH exposure, even within adolescence, influences its neural effects in females.

neuroscience↗

Effects of combined exposure to ethanol and delta-9-tetrahydrocannabinol during adolescence on synaptic plasticity in the prefrontal cortex of Long Evans rats

Significant exposure to alcohol or cannabis during adolescence can induce lasting disruptions of neuronal signaling in brain regions that are later to mature, such as the medial prefrontal cortex (mPFC). Considerably less is known about the effects of alcohol and cannabis co-use, despite its common occurrence. Here, we used male and female Long-Evans rats to investigate the effects of early-life exposure to ethanol, delta-9-tetrahydrocannabinol (THC), or their combination on high frequency stimulation (HFS)-induced plasticity in the prelimbic region of the mPFC. Animals were injected daily from postnatal days 30 to 45 with vehicle or THC (escalating doses, 3-20 mg/kg) and allowed to drink vehicle (0.1% saccharin) or 10% ethanol immediately after each injection. In vitro brain slice electrophysiology was then used to record population responses of layer V neurons following HFS in layer II/III after 3-4 weeks of abstinence. We found that THC exposure reduced body weight gains observed in ad libitum fed rats, and reduced intake of saccharin and ethanol. Compared to controls, there was a significant reduction in HFS-induced long-term depression (LTD) in rats exposed to either drug alone, and an absence of LTD in rats exposed to the drug combination. Bath application of indiplon or AR-A014418, which enhance GABAA receptor function or inhibit glycogen synthase kinase 3{beta} (GSK3{beta}), respectively, suggested the effects of ethanol, THC or their combination were due in part to lasting adaptations in GABA and GSK3{beta} signaling. These results suggest the potential for long-lasting adaptations in mPFC output following co-exposure to alcohol and THC.

neuroscience↗

Effects of combined use of alcohol and delta-9-tetrahydrocannibinol on working memory in Long Evans rats

The increase in social acceptance and legalization of cannabis over the last several years is likely to increase the prevalence of its co-use with alcohol. In spite of this, the potential for effects unique to co-use of these drugs, especially in moderate doses, has been studied relatively infrequently. We addressed this in the current study using a laboratory rat model of voluntary drug intake. Periadolescent male and female Long-Evans rats were allowed to orally self-administer ethanol, {Delta}9-tetrahydrocannibinol (THC), both drugs, or their vehicle controls from postnatal day (P) 30 to P47. They were subsequently trained and tested on an instrumental behavior task that assesses attention, working memory and behavioral flexibility. Similar to previous work, consumption of THC reduced both ethanol and saccharin intake in both sexes. Blood samples taken 14h following the final self-administration session revealed that females had higher levels of the THC metabolite THC-COOH. There were modest effects of THC on our delayed matching to position (DMTP) task, with females exhibiting reduced performance compared to their control group or male, drug using counterparts. However, there were no significant effects of co-use of ethanol or THC on DMTP performance, and drug effects were also not apparent in the reversal learning phase of the task when non-matching to position was required as the correct response. These findings are consistent with other published studies in rodent models showing that use of these drugs in low to moderate doses does not significantly impact memory or behavioral flexibility following a protracted abstinence period.

neuroscience↗