The induction of catalepsy and hyperactivity by morphine administered directly into the nucleus accumbens of rats

The results indicate a differential involvement of forebrain structures with the biphasic motor behaviour induced by intracerebral injections of morphine and a usefulness of this agent to investigate the mechanisms involved in motor control.

Abstract

The injection of morphine (1–100 μg) into the nucleus accumbens of the rat caused dose-dependent changes in motor function. An initial cataleptic phase was followed by hyperactivity which was associated with a weak and periodic biting behaviour. Injection of morphine (1–50 μg) into associated brain areas (anterior and posterior regions of the olfactory tubercle, anterior caudate putamen, area preoptica, globus pallidus and ventricular system) failed to induce catalepsy or induce a catalepsy of comparable intensity to that observed after intra-accumbens morphine. The catalepsy induced by 12.5 or 50 μg intra-accumbens morphine was antagonised by nalorphine when administered s.c. (2.5–10 mg/kg) and by nalorphine (2.5–10 μg)_and naloxone (0.25–1.0 μg) when injected into the nucleus accumbens, by low doses of cyproheptadine (1.25–5 mg/kg i.p.) and by large and probably non-specific doses of atropine (10 mg/kg i.p.) and piperoxan (20 mg/kg i.p.). In relatively large doses haloperidol (0.25–1.0 mg/kg i.p.) potentiated morphine (3.125 μg) catalepsy whereas α-methylparatyrosine reduced or failed to modify the morphine (1–50 μg) response. It is considered that the catalepsy induced by intra-accumbens morphine is due to a significant action within that nucleus which directly or indirectly involves an enhanced serotonergic activity. The subsequent hyperactivity phase induced by intra-accumbens morphine was markedly reduced by α-methyl-p-tyrosine pretreatment (250 mg/kg i.p.) and the biting component was abolished. The hyperactivity was more sensitive to the antagonistic action of α-adrenoceptor blocking agents piperoxan (10–40 mg/kg i.p.), aceperone (1.25–20 mg/kg i.p.), piperoxan (6.25–25 μg intra-accumbens) and phentolamine (1.25– 10 μg intra-accumbens) than fluphenazine (1.25–2.5 mg/kg i.p.), whilst the biting was inhibited by both the α-adrenoceptor blocking agents and fluphenazine. These data suggest that whereas the hyperactivity induced by intra-accumbens morphine primarily involves an enhanced noradrenergic action, the biting effect involves both noradrenaline and dopamine. However, it is uncertain as to whether mechanisms within the nucleus accumbens or associated areas are primarily or jointly involved as substrates for this effect, for whilst injections of morphine (1–50 μg)_into the anterior alfactory tubercle failed to induce hyperactivity, injections into the anterior caudata putamen and globus pallidus evoked a weak response, and injections into the posterior olfactory tubercle and area preoptica induced marked hyperactivity associated with weak biting. An assessment of the diffusion of (N-methyl-14C)-morphine on intra-accumbens injection, and particularly at the time when the hyperactivity phase was apparent indicated an ability to reach and more speculatively influence other than brain areas. This would emphasise that an extra-accumbens site of action for the mediation of the hyperactivity/biting effects cannot be excluded. The results indicate a differential involvement of forebrain structures with the biphasic motor behaviour induced by intracerebral injections of morphine and a usefulness of this agent to investigate the mechanisms involved in motor control.