Residual performance impairments in adult rats trained on an object discrimination task subsequent to cocaine administration during adolescence

Abstract

The present study was conducted to determine whether cognitive impairments in adult rats treated with cocaine during adolescence demonstrated in previous investigations extend to tests of object discrimination learning. Accordingly, 30-day-old male Long-Evans rats were injected subcutaneously with either 10 or 20 mg/kg cocaine or received control injections of saline for 7-8 consecutive days. An extended abstinence period was then introduced (mean = 70.7 ± 9.8 days) before subjects, who were now young adults (mean = 106.3 ± 10.2 days old), were assessed for acquisition of a two-choice object discrimination task. Using a correctional learning procedure conducted in a water maze, subjects were trained (eight trials per day for 10 days) to approach one of two multi-dimentional 'junk' objects. Although all animals acquired the discrimination to a reasonable extent, cocaine-treated subjects exhibited lower percentages of correct choices over the course of training (10 mg/kg = 59.6 ± 7.2% and 20 mg/kg = 59.4 ± 4.9%) relative to the saline control group (67.5 ± 4.9%). Further analyses revealed that saline-treated subjects acquired proficient discrimination performance earlier during the course of training, achieving an approximate 72% performance rate after only 3 days of training. This was in contrast to the two cocaine-treated groups needing 7 days of training to achieve comparable levels of performance. In addition, saline-treated subjects required significantly fewer trials (20.8 ± 8.9) than either cocaine-treated group (10 mg/kg = 52.2 ± 11.9 and 20 mg/kg = 63.3 ± 8.7) to reach an 87.5% correct response criterion (i.e. 7-correct-out-of-8-consecutive-trials) and performed at a higher above-chance level (13.5%) than either cocaine-treated group (3.6% and 5.3% for the 10 and 20 mg/kg cocaine groups, respectively). These findings demonstrate the existence of cognitive impairments in adulthood subsequent to cocaine exposure during adolescence despite a prolonged drug-free interval. Speculation regarding the neurobiological basis for this effect, especially with regard to alterations to prefrontal circuitry, is provided.

The effects of cocaine exposure in adolescence: Behavioural effects and neuroplastic mechanisms in experimental models

“…However, for drugs of abuse, the length of withdrawal may play a major role as the deriving negative emotional state may impinge on cocaine‐induced cognitive deterioration further worsening the pathological outcome. Accordingly, Santucci and Rabidou (2011) have shown that exposure of PND 30 rats to cocaine (10 or 20 mg kg −1 ) for 8 days induces cognitive impairments in early adulthood (Santucci & Rabidou, 2011). In this experiment, the authors tested the animals for the acquisition of a two‐choice object discrimination task.…”

The effects of abused drugs on adolescent development of corticolimbic circuitry and behavior

“…Human stimulant abusers, who usually initiate drug use in adolescence, have been shown to exhibit significant cognitive deficits that vary in magnitude depending on the duration of drug exposure (Bolla et al, 1998; Verdejo-Garcia et al, 2006). In adult rats exposed to psychostimulants during adolescence, there is evidence of enduring deficits in cognitive tasks that assess attention, fear learning, memory, decision making, and impulse control (Harvey et al, 2009; Santucci and Rabidou, 2011; Sillivan et al, 2011; Hankosky and Gulley, 2012). However, in these studies, it is difficult to ascertain if adolescents are relatively more sensitive to these effects because comparison groups of adult-exposed subjects were rarely utilized.…”

Impact of cannabidiol on brain glucose metabolism of C57Bl/6 male mice previously exposed to cocaine

“…studies, cocaine was associated with deficits in attention, episodic memory, and working memory with moderate and large effect sizes magnitude (Potvin et al, 2014). Hippocampal-dependent cognitive impairment during withdrawal is also well documented in preclinical models (Fijał et al, 2015;Fole et al, 2015;Jordan & Andersen, 2018;Krueger et al, 2009;Ladrón de Guevara-Miranda et al, 2017;Mendez et al, 2008;Mottarlini et al, 2020;Preston et al, 2019;Santucci & Rabidou, 2011). Although these studies were performed with prolonged cocaine administration (8-14 days) than that used in the present study, considering the increase in glucose metabolism induced by CBD in regions known to be affected by cocaine withdrawal, and its neuroprotective profile, we can suggest the benefit of CBD in improving cognitive function of individuals undergoing detoxification.…”